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LOW FREQUENCY VIBRATION ASSISTED BLOOD PERFUSION
EMERGENCY SYSTEM
1. TECHNICAL FIELD
This invention relates to noninvasive medical systems for imparting
transcutaneously applied low frequency mechanical vibrational energy to the
human
body to improve first line emergency treatment of acute thrombotic vascular
obstructions. More particularly, this invention relates to non-invasive drug
delivery
systems to improve delivery of systemically administered clot disrupting and
vasodilatory medications to acutely obstructed blood vessels.
2. BACKGROUND OF THE INVENTION
Acute vascular obstructions, ischemia and infarction are conunon medical
concerns. Acute Myocardial Infarction ("AMT') subsequent to coronary
thromboses in
particular is one of the leading causes of death in North America. Current
first line
treatment of thromboses in the acute phase when the patient reaches
professional care is
typically by intravenous introduction of thrombolytics, or a combination of
drugs such
as heparin, aspirin and/or GP 2b 3a platelet inhibitors to dissolve the blood
clot.
Intravenous and oral nitrates may also be introduced in order to dilate the
culprit
coronary or other vessel, which usually has a degree of spasm associated.
Thronibolytic drug treatment does not, however, have a high success rate. The
success of systemically delivered IV drug therapy in increasing reperfusion
rates in the
treatment of ST elevation AIVII is discussed in the following publications:
1.) American Heart Association, Satellite Symposium 73rd Scientific Session,
St.
Michael's Review, New Orleans, Louisiana; Nov 11, 2000.
2.) Francis W M.D., "Ultrasound - Enhanced Thrombolysis." Echocardiography: A.
Jrnl. of CV Ultrasound & Allied Tech. Vol. 18, No. 3, 2001. pp 239 - 246.
3.) Sanbom T et al., "Impact of Thrombolysis Intra-aortic Balloon Pump Counter
pulsation and their Combination in Cardiogenic Shock Complicating Acute
Nlyoca'rdial
Infarction.", SHOCK REGISTRY JACC, 36 (3) Suppl. A. 2000, 1123 - 9.
The American Heart Association, Satellite Symposium 73rd Scientific Session,
St. Michael's Review reported reperfusion rates (i.e. TIIVII 3 flow @ 60 - 90
minutes)
with standard thrombolytic therapy varying between 50 and 63%.
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Francis reported that lytic therapy fails to achieve any reperfusion (at all)
in up
to 20% of patients.
Success with drug based reperfusion treatment and in-hospital survival
declines
markedly when the patient becomes hemodynamically unstable or enters
cardiogenic
shock, which is the leading cause of in-hospital deaths from ivII in North
America.
Sanbom et al. report 63% in-hospital mortality despite the use of thrombolytic
therapy.
In the case of ST elevation Acute Myocardial Infarction, when noninvasive drug
treatment (i.e. systeniically introduced IV thrombolysis) to achieve
reperfusion fails,
invasive catheter based techniques such as Percutaneous Coronary Intervention
("PCI")
are employed. Sometimes, PCI is chosen as a direct measure, whereby a
coordination of
the immediate use of lytics or other agents may be first established in the
field while en
route to a cardiac catheterization laboratory where intervention can be
performed. A
disadvantage of invasive treatment for acute thrombotic obstructions (while
very
successful) is the infrastructure required, particularly the cardiac "cathlab"
requiring
substantial equipment and staff. Such infrastructure is not readily accessible
in hospitals
world wide, and even when available, there is a significant time requirement
to
coordinate and set up equipment and personnel. Due to the lack of immediate
availability of cathlabs, patients, often unstable, must be transported and/or
wait for the
cathlab team to assemble. These difficulties result in a delay in treatment
increasing
myocardial necrosis, and reducing the likelihood of a successful and timely
reperfusion.
Treatment systems utilizing noninvasive vibration in the low frequency
ultrasonic range ("LFUS" e.g. 20 kHz - 100 kHz) have been employed as an
adjunct to
systemically delivered IV thrombolysis including coronary thrombolysis, in
attempting
to overcome these disadvantages. The LFUS wave form provides mechanical
agitation
via cavitation and acoustic. streaming to the blood within the culprit
vasculature wherein
a blood clot resides, thereby encouraging disruption of the clot and increased
permeation
of the drug into the clot to accelerate reperfusion.
LFUS to disrupt tluoniboses and assist thrombolysis, has however, only shown
effectiveness in research applications (i.e. animal studies), for the
treatment of relatively
superficial thromboses, where the exact, fixed location of the blood clot was
already
known to the investigator. LFUS wave forms (which deliver low amplitude micro
displacemebts which are imperceptible to a patient) offer no assurance of
therapeutic
ultrasonic penetration to reach a blood clot within a human body in a
practical
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application, without, for example, the establishment of a viable acoustic
energy delivery
window and targeting via direction of an application probe (i.e. as in
ultrasonographic
imaging), which takes intelligible application of force and angulation of the
probe
against a patient's skin via a skilled operator. The subsequent resultant need
for high
skill to direct a LFUS application makes such a therapy a poor candidate for
emergency
cases where a skilled treatment operator would rarely be available. A non-
directed
LFUS treatment (without a skilled imaging approach) in particular, is poorly
suited
towards human coronary applications as the human heart is a relatively deep
structure, is
located variably within the thoracic cavity, and the blood clot is a hidden,
moving target
located beneath higlily attenuating anatomic structures such as lung, fat and
dense
intercostal muscle which does not transmit ultrasound.
Thompson, T. et al in US Patent Appl. 20020049395 - 2002, disclose the
emergency application of a non-directed LFUS treatment in conjunction with
thrombolytic therapy in response to Acute MI in humans, wherein LFUS is
delivered in
a nonspecific manner to a patients skin surface through a liquid cooling
medium without
intelligible placement and direction of the ultrasonic source through a
confirmed
ultrasonic penetrating window. As stated this method is sub-optimal as it does
not
insure adequate penetration of the therapeutic signal, and no proof is
provided that this
style of technique will show a clinical benefit in humans. Further examples of
this kind
of noninvasive LFUS treatment for vascular thromboses are disclosed in US Pat.
Nos.
6126619, 5713831, 5879314, 6126619, and 6398772; as well as in US Pat. Appl.
Nos.
20020082529, 20020107473, 20020072691, 20020055693, 200200726690 and
20020091339.
Non-invasively delivered ultrasonic treatment systems directed by skilled
medical imaging techniques to disrupt an undesirable target (including
throniboses),
have been disclosed in numerous articles and publications.
Carter and Siegel in US Patent. No's 5509S96 and 5695460 respectively,
disclose an externally applied LFUS treatment probe placed in direct contact
with a
patient's skin (with optional means to enable "directing" or "focusing" of the
LFUS
wave form towards the area or volume targeted) to improve emergency
thrombolysis,
including coronary thrombolysis. A thrombolytic agent and / or cavitating
micro bubble
solution is preferably introduced by a catheter placed "proximate" the site of
the
vascular obstruction, to ensure effectiveness of the treatment system. The
requirement of
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high skill (both in directing the treatment probe, and in the invasive
procedure of
introducing a catheter) is not ideal (nor preferable) for first line therapy
applications in
the field or in the emergency room. Furthermore the probe contact will
typically
overheat and cause burning of the patient's skin.
Lithotriptic style techniques such as in US Patents 5065741, 5207214, 5524620,
5613940, 5725432, 6068596 and US Patent AppL 2004/00062S8 Al (which employ use
of externally imparted focused ultrasonic waves or ultrasonic shock waves
directed by
an imaging modality to disrupt an internal target including thromboses) have
also been
disclosed. This style of therapy (while common in the treatment of kidney
stones and
the like) has not gained acceptance in the emergency treatment of acute
vascular
obstructions or thrombotic obstructions, probably because thrombotic lesions
are
difficult (if not impossible) to conveniently image, and these style of
applications are
inexpedient for use as they require advanced training, a controlled
environment,
calculations, and specialized equipment to employ. Furthermore, lithotriptic
systenis
and other focused wave therapy techniques are generally limited to treatment
of
stationary targets within the human body, hence applications to the coronary
arteries
(such as in the acute treatment of coronary thrombotic lesions) cannot
prospectively be
performed.
Low frequency mechanical vibration treatment systems have been considered in
the invasive treatment of thrombotic obstructions via catheter based
techniques. U.S.
Patent No. 6,287,271 to Dubrul et al., for example, discloses a low-frequency
(1-1000
Hz) vibrating catlieter drug delivery system resulting in 68% lysing when
placed
proximally to an artificial clot in a test tube with the drug Urokinase,
versus 4.5% lysing
with Urokinase treatment alone. As stated above, this systeni is invasive, and
thereby
requiring great specialized.skill and equipment to introduce a catheter
directly to the
thrombosis site, and thus has no utility as a first line measure in the field
or in
emergency room cases.
Generally, non-invasively delivered low frequency vibration or percussion in
the
sonic to infrasonic ranges has received little focus in the field of treatment
of acute
vascular obstructions, ischenzic events or blood flow disturbances.
Cardio Pulmonary Resuscitation ("CPR"), which is essentially high
displacement amplitude compressional wave energy of 1.5 Hz (i.e. very low
frequency
vibration), was paired used successfully in conjunction with coronary
thrombolysis in
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cases of known acute myocardial infarction which had deteriorated and a poor
outcome
was otherwise imminent. These cases were reported by Tiffany et al. in "Bolus
Thrombolytic Infusions During CPR for Patients With Refractory Arrest Rhythms:
Outcome of a Case Series" (Annals of Emergency Medicine, 31:1, Jan 1998, 134 -
136).
This medical method, which was designed to sustain the life of the patient
conjointly
with the deliverance of thrombolysis (and not to act as an adjunct to
thrombolysis per
se), is limited to cardiac arrest situations, and the manual nature of the
application of
high displacement amplitude, mechanical energy by human hand would be labor
intensive, potentialIy tiresome to an operator, and would eventually cause
undue harm to
a patient if delivered for sustained periods.
Wobser, E et al. in an article "Intragastral Disintegration of Blood Coagula
by
Mechanical Vibration" in Endoscopy 10, 1978, 15 - 19; discloses a 50 - 500 Hz
"flexural electromagnetic resonator" for insertion into the stomach for
disruption of "big
blood coagula in order to facilitate endoscopic examination in GI bleeds.
Furthermore,
Lee in US Patent No. 5,676,637 discloses a low frequency vibratory probe for
insertion
in the anus to dissolve venous thromboses to improve blood circulation in the
treatment
of hemorrhoids. Neither system is directed towards treatment of acute vascular
blockages or emergency blood flow disturbances, and neither instrument is
configured to
enable effective penetration through a significantly attenuating barrier such
as the chest
wall or other external body surface.
Matsuura in US Patent No. 6,424,864 B1 discloses an all purpose wave therapy
system (i.e. applying electric, electromagnetic and / or acoustic waves) for
treatment of a
plurality of ailments ranging from depression, to rheumatism, to infertility,
to poor blood
circulation in.the hands and feet. In one disclosed embodiment, sound waves
generated
through one of a sonic platform apparatus or set of head phones enables
acoustic therapy
to the body (or "cuticle", or "ears") of a user in contact with the apparatus.
The `864
patent describes a low intensity, dissipated therapeutic system of acoustic
and
electromagnetic wave transmission to a user, and is thereby not suitable to
emergency
disruptive and agitative applications wherein the impartation of highly
concentrated
extemal percussive force to predetermined or selected application sites is
required to
ensure therapeutic penetration and effectiveness. Furthermore, this system is
not
prescribed towards the treatment of acute vascular obstructions or ischemic
events,
hence there are no methods by which these particular applications could be
performed.
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Randoll in US Patent No. 6,579,251 B1 discloses a low frequency oscillatory
device for the treatment of a plurality of ailments including "niicro
circulation
disorders", employing a rotating eccentrically mounted treatment head which
effectively
delivers (when rotating) oscillatory skin displacements of between 4 to 7 mm
at a
frequency of 5 - 25 Hz to its user. The `251 patent mimics patient "tremors"
to drive
sequestered fluids through the valved systems of the veins and lymphatics to
clear tissue
spaces. Such rotating head devices are not designed nor intended for the
emergency
treatment of acute blood flow disturbances, and are energy inefficient as the
forces of
vibration are directed tangentially to the skin surface.
Endo, Y in GB2167961 discloses a bed (or mattress) sheet with a plurality of
vibrating members to be applied to the body surface of a user while sleeping,
for several
uses ranging from reduced "sleep latency" to the prevention of "interruption
in blood
circulation". The "961 patent is not directed to emergency applications or
response to
ischemic events, and the vibration disclosed is ineffectual as it is of low
amplitude and
cannot be concentrated to a particular body part afflicted.
Cossone, A. et al. in PCT Appi. WO 02/0782 A2, and US Patent No. 6,500,134
B1 discloses a water-bath vibrating palliative, therapeutic system, with an
optimal
frequency of 600 Hz to generally improve coronary artery circulation in
chronic cases.
This water bath method is not designed (and is impractical) for use in the
field and
prospectively for heart attack or acute cases, and the water to skin
vibrational coupling is
energy transmission inefficient, of low amplitude, and does not enable
focusing of
treatment to key area's upon the chest wall or other body part which would
confer
maxinium benefit.
Nagy in European Patent Appl. No. 0429109 B 1 and US Patent No. 5,291,894
discloses a loud speaker system operational to generate acoustic waves (i.e.
sound waves
through air) in the 1- 1000 Hz and 20 Hz - 20 kHz range respectively, for the
chronic
degenerative treatment of vasoconstrictions resulting in poor circulation and
stasis to the
limbs of a patient. Nagy also names, in short, the optional use of a
"piezoelectric
element" which may alternatively be placed in direct contact against the body
part
treated. Sound waves through air are a highly inefficient means for delivering
mechanical energy to the human body (i.e. the forces produced to the skin
surface
treated would be negligible), and there is no proof provided that this style
of therapy
would assist blood circulation in acute or chronic cases. Similarly
"piezoelectric
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elements" (which are generally used to emit micro displacements in the
ultrasonic
ranges), are not operable to independently generate high displacements under
load (i.e.
in the low frequencv ranges), hence cannot.supply (prospectively) the
agitarive
percussive force or mechanical energy required to ensure therapeutic
penetration and
effective treatment in emergency thrombotic applications which are often
deeply
situated.
Saclater in US Patent Appl. 20020103454 discloses a "vibrating" "reciprocating
movement platform" or bed which oscillates in a to and fro motion (i.e. in the
head to
foot direction), delivering "etternal pulses" to a human body in the frequency
range of
0.25 - 6 Hz, for a plurality of applications including improving blood
circulation in
chronic and acute cases. The `454 patent application invokes hemodynamic
forces or
"pulses" by virtue of the accelerations and deceleration's of the movement
platform
which purportedly instill slieer stresses from blood to endothelium of the
vasculature,
which is 1.-nown to invoke the liberation of endogenous "beneficial mediators"
such as t-
PA, EDRF, and Nitric Oxide (all of which are of assistance in the improvement
of blood
flow and prophylaxis to disease). Whole body "vibration" methods such as
Sackner
describes are not well suited for treatment of acute thrombotic lesions or
emergency
blood flow disturbances as relatively small (or insigrtificant) localized
forces to the
targeted vascular regions themselves are generated. Furthermore, the
oscillations
emitted are lower than the resonance frequency of the heart within the
thoracic cavity,
hence the vibratory effect to the heart (and coronaries) would be even further
diminished
in cardiac applications. Finally the treatment method invariably also shakes
the patient's
head which is potentially dangerous and inappropriate if the treatment system
wliere
ever to be used conjointly with thrombolvtic therapy.
Jap. Pat. No. JP 8,089,549 ("549") to Koiwa and Honda discloses a noninvasive
50 Hz diastolic timed chest wall vibrator treatment system via a singular
mechanical
probe to skin coupling interface to treat cardiac ischernia. The `549 patent
increases
cordnary blood flow to stable patients with known coronary artery narrowings,
through a
prescribed method of applying vibration specifically tinied to the diastolic
phase of the
cardiac cycle via a hand held unit applied to the chest wall.in a low
amplitude,
comfortable maimer (i.e. such that the patient "experiences no pain"). Koiwa
teaches
that diastolic timed vibration relaxes the myocardium (which is particularly
stiff in
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ischemic states), allowing it to perfuse more efficiently and thereby assist
blood
perfusion to the ischemic heart.
The `549 patent is not directed to the treatment of emergent coronary
incidents
or acute tlirombotic events, hence there are inherent liniitations to the
disclosed system.
For example, the disclosed single probe to skin coupling is a sub-optimal
nieans of
vibration to chest wall transmission and penetration, there is no provision
for the
delivery of vibration at high amplitude to ensure therapeutic penetration
(without for
example a skilled iniagina or nionitoring systeni), and the timed application
of vibration
limits its effectiveness as there is no vibration during systole. The comfort
level of the
patient, and timing of vibration specific to diastole. is of lesser importance
(and in fact
limiting) when the key point of the therapy is to agitate and disrupt a
thrombus, as well
as to encourage the mixing of drugs into the thrombus. Furthermore, complex
monitoring and processing means via an electrocardiographic trigger are
required to
effect cardiac phase controlled varying vibration, thus the treatment system
is sonlewhat
awkward and difficult to use prospectively in emergency cases.
Low frequency vibrators or percussive devices of high power and displacement
enablement are well known (e.g. for massage and mobilization of pulmonary
congestions), but have found no utiiity in the treatment of acute vascular
obstructions or
response to ischemic events. These devices (such as the Mini Pro 2 ThumperTrt,
Homedics Professional Percussion Massager, and the "Deep muscle stimulator
device"
disclosed in US patent 6,682,496), while of potential employment to the
current
specification, are not ideal as they are equipped with one, non-adjustable
high
displacement amplitude setting, so their vibrations may be either too strong
or too weak
depending on the body surface and tolerance level of the patient treated.
Also, such
devices are known to quickly overheat and dampen oscillations when placed
under load,
which greatly diniinishes their overaII penetration power and application
tinie.
Vibration devices with incrementally selectable force or power control (i.e.
at a
given frequency) have been generally described for a variety of inedical uses
ranging
from penile stimulation (US 6,027,444), gum nzassage (US 3,664,331), fingertip
massage (US 21 S 1252, US 149S680), assisting the diffusion of hair solutions
into the
scalp of a user (US 5,830,177), eliminating mucus from the lung (US 5,453,0S
1), and for
treatment of scoliosis of the spine (US 6,082,365). These devices have not
been
optimally combined however, with a high powered vibration source (i.e. one
adapted to
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emit a high displacement amplitude while under load) and an optiniized
attachment
interface (i.e. enabling concentrated delivery of vibration localized to a
selected body
surface), to enable an effective, penetrative vibration delivery system
suitable for
treatment of acute vascular obstructions, which are often deeply situated
within the
human body.
Harris et al. in US patent Appl. 2002/0161315 Al discloses a low frequency
hand held percussive massaeer of.indeterminate power (which purportedly
enables at
least marginal levels of force or intensity emission control), comprising a
first vibratory
massage element mounted to one side of the massage body and a pair of
percussive
"nodes" mounted to the opposite side. While of potential use to the current
specification, the disclosed massager is not ideal as the placement and
necessary
operation of a vibratory elenlent in diametric opposition to the percussive
nodes is
energy inefficient, and is inexpedient for use as it makes the device
difficult to apply
with significant engagement=force by the hands of an operator. Furthermore the
disclosed massager does not allow for the particular selection of variable
stroke length
or waveshape control, which may be advantageous in a controlled research or
clinical
setting wherein definable, variable, and reproducible percussive stimuli may
be desired.
High powered low frequency oscillation devices operable under load with
moduable vibratory wave forms (including selectable intensity and even wave
shape) are
known to industry, but have found no common use in direct human contact for
application to selected body surfaces, hence the oscillations imparted would
be either
indirect and dissipated, or fundamentally unsafe to apply. E,Yamples of such
vibration
sources consist of: Aura Bass Shakers, Clark Synthesis Tactile Sound
Transducers,
industrial linear motors, speakers (i.e. voice coils -"woofers"), and pile
drivers.
There has also been little focus in the area of directing or confirnii.ng the
penetration levels of low frequency vibration (or percussion) to an invasively
located
target in a patient, via an imaging or monitoring technique.
Japanese Pat. No. JP 4156523 to Takishima et al. discloses a miniaturized
accelerometer disposed on a transesophageal lead for nionitoring penetration
levels of
externally imparted cardiac phased modulated vibration to the heart, to
facilitate the
diagnosis and treatment of heart failure. The requirement of an invasive step
of
introducing a transesophageal probe to enable vibration monitoring and
targeting is not
ideal (nor preferred) in emergency settings.
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US Pat. No. 6,068,596 to Weth et al. discloses an ultrasonic shock wave
eniission device coupled to an ultrasonic imaeing probe to focus and direct
ultrasonic
shock waves to internalized neural clusters in chronic pain management. The
`596
patent is not directed towards treatment of thromboses or acute vascular
obstructions,
and the resultinQ "pulsed" waves (which are only emitted once every couple of
minutes)
are in the ultrasonic range hence are of low amplitude and must be focused to
yield a
significant internal effect. Furthermore the ultrasonic imaging probe is not
utilized to
emit the therapeutic ultrasonic shock waves, hence an optimal acoustic (or
penetration)
delivery window through the overlying body surface is not established.
LIS Pat. No. 5,919,139 to Lin discloses a low amplitude (designed for "gentle
percussive hitting or vibrating") soni.c vibration source mounted side by side
to an
ultrasonic imaging transducer for diagnostic purposes, which enables
visualization of the
invasive target vibrated. This device is not designed for therapy, and is
inexpedient for
use (prospectively) in the location and disruption of tissue targets, as the
sonic vibration
source is not advantageously placed in the same position as the ultrasonic
imaging probe
upon the body surface, such as to conveniently enable an operator direct
visualization
and targeting of vibration through an optiniized sonic penetration window
proximate the
vascular target.
As can be seen from above, there is an ongoing need to optimize a noninvasive
system for the treatment of vascular ischemia and infarction by drug therapy
and / or
transcutaneously delivered mechanically therapeutic techniques. The prior art
has failed
to provide a simple to use, noninvasive niechanical method and apparatus that
reliably
ensures sufficient penetration to the culprit vessels and sites of vascular
thromboses (in
particular to the deeply situated vessels within the thoracic cavity such as
the coronary
arteries) to ensure an adequate agitative and disruptive therapeutic effect in
emergency
cases. Furthemiore, none of the prior arts have successfully integrated a
systenzically
delivered drug therapy system, and / or the optional use of a practical
noninvasive
imaging system for targeting therapy, to optimally enable such an apparatus.
There is accordingly a need for an effective and easy to apply emergency
response system in the application of noninvasive, therapeutic mechanical
energy to the
human body for the treatment of acute vascular obstructions. The system should
be
optionally portable to enable reaching a victim in the field, employable with
drugs, and
preferably adaptable to suit the expertise of an operator (i.e, with the
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incorporation of a practical and convenient imaging system) whose skill level
and
experience (and thereby preferred clinical approach) may vary markedly.
3. SLiNLILARY OF THE IiYVENTION
The present invention relates to a first line emergency response svstem for
the
treatment of acute thrombotic and / or vasospastic vascular obstructions via
the
noninvasive, high amplitude application of low frequency vibration in the 1-
1000 Hz
range. The emergency response system optimally utilizes vibration as an
adjunct to
systemically administered drug therapy. The present invention is based on the
intuition
that extemal, transcutaneously iniparted low frequency vibration at a high
force or
displacement amplitude can penetrate deeply within the human body and into the
vasculature, without a requirement of undue skill (or imaging techniques), and
provide a
mechanical disruption of thromboses and synergistic support to systemically
delivered
drug therapy to improve localized drug effectiveness.
The preferred embodiment relates to an emergency response system employing a
low frequency vibration blood perfusion apparatus designed to facilitate and
improve the
emergency treatment of acute ST elevation myocardial infarction, by externally
imparting high amplitude sonic to infrasonic mechanical energy to the chest
wall of a
patient as an adjunct to systemically delivered thronibolytic therapy, (and /
or any otlier
form of drug therapy). A noninvasive vibrator comprising a vibration source
with an
attachment interface (to enhance transmission and / or effectiveness of
emitted
vibration), enables high aniplitude low frequency external vibration to
optimally
penetrate to the heart, without the requirement of a sl:illed imaging
technique, and
thereby synergistically facilitate the action of systemically directed drug
therapy by
providing an agitative response to the culprit coronary circulation. Agitation
of the
epiniyocardium by vibration stimuli, and lience the coronary arteries, will
improve (by
way of sonic streaming, sheer forces and cavitation) the mixing of
systemically
introduced drugs down an otherwise zero flow, or low flow vascular system.
Mechanically delivered vibration further induces disruption of clots which
leads to
increased permeation of drugs into the clots, and also low frequency vibration
independently results in a localized coronary vasodilatory response to the
culprit
circulation which often has a degree of spasm associated.
A practical emergency response system employing a high powered extemal low
frequency mechanical vibrator, optimally employable in conjunction with
systemically
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delivered drug therapy and operational in the low frequency ranges (i.e. <=
1000 Hz
range), which is specifically designed and suited to assist the localized
process of
coronary thrombotic disruption'and thrombolysis (and relief of coronary spasni
if
associated) in the particular emergency treatment of Acute Myocardial
Infarction, is
disclosed.
The provided system is further adaptable to assist clot disruption and
systemically delivered drug therapy and effectiveness localized to other body
regions
experiencing an acute state of low blood perfusion, such as in acute vascular
obstructions to the cerebral, pulmonary and peripheral vasculature.
A first aspect of the present invention is to provide a system and a preferred
apparatus enabling an easy to impart, non-skilled based vibration therapy,
comprising
the steps of placing a vibrator non-invasively (without an imaging modality)
to a
selected body surface deemed proximate to a culprit vascular obstruction, and
applying
low frequency vibration at a high force or displacement amplitude to the
selected body
surface, preferably as an adjunct to systeniically administered drug therapy.
A second aspect of the present invention (as a means to optimize the system),
provides methods and apparatus to the incorporation of ultrasonic imaging,
which
enables a "skilled" operator (when available) to intelligibly direct
etiternally imparted
vibration in a relatively easy and portable manner towards an invasive target.
As a third
aspect of the present invention (and as a means of further optimizing the
systeni),
methods and apparatus enabling cardiac phase controlled vibration delivery is
additionally provided, which may be of use in cardiac applications, when or if
the
patient deteriorates to a state of cardiogenic shocl.
A fourth aspect of the present invention is to integrate the foregoing into an
effective emergency response system (and method of vibration assisted drug
delivery)
for treatment of acute vascular obstructions. The system is optionally
portable to meet
the needs of first line emergency treatment in the field, employable with
dzugs, and
adaptable to meet the needs of differing operators with varying levels of
training and
skill.
Vibration of a clot disruptive drug improves diffusability and penetrability
of
said drug, such as to enable a synergistic system of vibration assisted drug
delivery.
It is accordingly a general object of this present invention to define a
utility for
extemally placed, high amplitude, low frequency vibration to the thorax of a
patient, as a
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synergistic adjunct to systemically delivered drug therapy, in a cardiological
treatment
application associated with acute myocardial infarction.
It is a further object of the present invention to provide an emergency
response
system whereby 1 -1000 Hz., (or preferably 1-120 Hz and optimally 20 - 120 Hz
compressional waves) are applied externally at high force and displacement
amplitude to
the chest wall of the patient, to act to as an adjunct to systemically
introduced drug
therapy in the first line treatment of acute ST elevation myocardial
infarction.
It is a further object of the present invention to provide an emergency
response
system which is adaptable to provide extemally imparted, high amplitude low
frequency
vibration to improve drug therapy and localized drug effectiveness to a
variety of body
regions suffering from an acute, emergent state of low blood perfusion, such
as the body
regions of the brain, lung, and the periphery.
It is a further object of the present invention to provide an emergency
response
system which is simple and easy to use, without a skill requirement beyond
what a
nurse, paramedic, or even the patient (i.e. by self administration) could
typically
provide.
It is a further object of the present invention to provide a preferred higher
powered vibrator with a higher force and displacement aniplitude potential for
vibration
delivery to selected body surfaces than what has been described in the prior
art, in
recognition that a potential degree of overlying soft tissue injury such as a
bruise or a
degree of patient discomfort, is of small consequence relative to the gains of
an
improved thrombolysis in an emergency situation to restore vessel flow to a
major
infarcting internal organ such as the heart.
It is a further object of the present invention to provide a preferred
vibrator of
the aforementioned type which is of a size and shape to enable hand held
operation, such
as to add portability, maneuverability, and ease of placement of the vibrator
to varying
body surfaces, as well as a moduable or controllable means of applying
engagement
force by the hand or hands of an operator.
It is a fiuther object of the present invention to provide a preferred
vibrator of
the aforementioned type with an amplitude regulating mechanism, such as to
enable a
manual adjustnient of displacement amplitude or force of vibration emitted to
a
tolerance level of a patient, which may be very low or very high depending on
the body
surface and constitution of the patient treated.
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It is a further object of the present invention to provide a prefen-ed
vibrator of
the aforementioned type which is operable to a broad range of selectable
frequency.
amplitude and wave form parameters, such to enable an effective research as
well as
clinical tool.
It is a further object of the present invention to provide a vibrator with a
selection of vibration / body surface attachment interfaces, such as to
accommodate a
preferred method and / or skill level of an operator in order to enhance
vibration
transmission and effectiveness.
It is a further object of the present invention to provide a vibration / body
surface attachment interface of the above type, comprising at least one
contact (or
contact node) adapted in size and shape to enable efficient seating within a
rib space of a
patient in order to optimize vibration transmission to the chest wall and
vascular
structures within the thoracic cavity.
It is a further object of the present invention to provide an vibration / body
15' surface attachment interface of the above type, comprising a pair of
contacts (or contact
nodes) such as to enable contact at a pair of application sites preferably
bridging the
sternum of the patient, in order to improve penetration to the mediasteinal
cavity, and
match the anatoniic configuration of the base of the heart wherein the
coronary anatomy
is substantially distributed.
It is a further object of the present invention to provide a vibration / body
surface attachment interface of the above type, comprising a plurality greater
than a pair
of contacts (or contact nodes) wherein pairs of contacts are grouped together
bridging an
elongated support structure at adjustable levels, such as to enable contact at
a plurality
of application sites (or intercostal space levels) preferably bridging the
sternum of the
patient, in order to maximize penetration to the heart which is variably
situated
depending on the anatomy of the patient.
It is a further object of the present invention to provide a vibration / body
surface attachment interface of the above type, which in addition to supplying
the means
of transniitting low frequency vibration from a vibration source to a patient,
is
additionally enabled to provide ultrasonogcaphic imaging such that a skilled
operator
(when available) may optimize penetration and target vibration to a culprit
vascular
region or target area while concurrently imaging the target.
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It is a further object of the present invention to provide a vibration / body
surface attachment interface of the above tvpe, which in addition to supphing
the means
of transmitting low frequency vibration from a vibration source to a patient,
is
additionally enabled to emit a tlierapeutic low frequency ultrasonic wave form
such as to
provide a pair of therapeutic oscillating wave forms (i.e. low frequency
vibration plus
low frequency ultrasound) in concert.
It is a further object of the present invention to provide a vibration ! body
surface attachment interface of the above type, which is not only enabled to
transmit low
frequency vibration from the vibration source and concurrently emit a low
frequency
ultrasonic treatment wave fomi (i.e. as above), but is additionally enabled to
provide
ultrasonographic imaging such that an operator may optimize penetration and
target low
frequency vibration and low frequency ultrasonic emissions to a culprit
vascular region
or target area while concurrently imaging the target.
It is a further object of the present invention to provide a mechanical and
adjustable engagement means to a vibrator coniprising a clamp, wherein the
clamp is
adapted to bedside or stretcher use to hold the vibrator against a patient's
body surface
(such as the chest wall or back), so an operator need not hold the vibrator in
place by
hand throughout the course of vibration therapy.
It is a further object of the present invention to provide a mechanical and
adjustable engagement means to a vibrator comprising a belt system, wherein
the belt
system is adapted to encircle a patient's body part (such as the thorax) and
hold the
vibrator against the body surface treated (such as the chest wall) so an
operator need not
hold the vibrator by hand, and so that the patient may sit up or even
ambulate.
It is a fiirther object of the present invention to provide a vibration method
and
apparatus for enabling cardiac phase controlled time and optionally frequency
varying
vibration delivery, to enable the selection of vibration timing=algorithms
desimed to
optinvze vibration of the heart and coronary arteries. Cardiac phase
controlled vibration
is of particular importance in cases of acute myocardial infarction which have
deteriorated into cardiogenic shock, wherein vibration timed exclusively to
the diastolic
cardiac phase provides a positive inotr opic effect in addition to mechanical
agitation of
the heart and coronary arteries.
It is a primary object of the present invention to provide a self-contained,
first
line, mobile eniergency response system and kit (and method of vibrarion
assisted drug
CA 02540439 2006-01-27
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delivery) for treatment of acute, emergent, thrombotic and / or vasospastic
vascular
obstructions by trained professionals (in the ambulance, before
transportation, or in
hospital), wherein the mobile, emergency response ldt comprises: a high
powered low
frequency vibrator, plus any one or conibination of; a selection of
interchangeable
~ attachment interfaces including those enablina ultrasonic imaging and low
frequency
ultrasonic therapeutic emissions, a drug delivery means, at least one and
preferably a
plurality of useful drugs to be delivered, a set of instructions indicating
method of use,
and a portable carrying case enabling storage and portability of the
aforenientioned
members. Options to the mobile, emergency response kit include: an engagement
means
(selectable between a clamp and belt apparatus), and a cardiac phase
controlled
vibration delivery system (to optimize the timing of vibration delivery
specifically for
cardiac applications, which is of special importance in the case where the
patient
deteriorates into a state of cardiogenic shock).
It is a final object of the present invention, to provide a self contained,
portable,
emergency response system and kit (and method of vibration assisted drug
delivery) for
outpatient community use, wherein the portable emergency response kit
comprises a
high powered low frequency vibrator, and preferably at least one anti-anginal
drug to be
delivered_ The portable einergency response kit is employable to a victini (or
bystander)
in the community for self (or assisted) treatment of chest pain refractory to
and / or
complimentary with conventional anti-anginal therapy (e.g. nitro spray, or
pill), wherein
an acute coronary event cannot be ruled out.
4. BRIEF DESCRIPTION OF THE DRANVINGS
The apparatus and method of the present invention will now be described with
reference to the accompanying drawing figures, in which:
Fi`=e 1 is a perspective view of a supine patient receiving treatment from an
operator held vibrator according to the invention.
Figure 2 is a perspective view of a supine patient receiving treatnient from a
clamped vibrator according to the invention.
Figure 3 is a perspective view of an attachment interface comprising a
bifurcated connector with a pair of support arms, each support arm having a
single
contact according to the invention.
Figure 4 is a perspective view of a variant attachment interface comprising a
bifurcated connector having a plurality of support atms according to the
invention.
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Figure 5 is a perspective view of a variant attachment interface comprising a
variant connector having two pairs of support arms according to the invention.
Figure 6 is a schematic diaggram of the preferred vibrator and its operable
components according to the invention.
Figure 7 is a schematic diagram of the variant cardiac phase controlled
vibrator
and its operable components according to the invention.
Figure 8 is a graphic illustration of a variety of vibratory displacement wave
fonns according to the invention.
Figure 9 is a perspective view of a variation of the vibrator incorporating
ultrasonographic imaging with treatment vibration via a hand held technique
according
to the invention.
Figure 10 is a perspective view of a variant ultrasonic imaging contact
according
to the invention.
Figure 11 is a perspective view of a variation of the clamp mechanism
according
to the invention.
Figure 12 is a perspective view of a patient in fowler's position receiving
treatment from a belt engaged vibrator according to the invention.
Figure 13 is a schematic diagram of the preferred vibration niethod for the
remediation of acute thrombotic vascular obstructions according to the
invention.
Figure 14 is a schematic diagram of a variation to the preferred vibration
method
employing ultrasonic imaging to direct vibration.
5. DETAILED DESCRIPTION AND PREFERRED EMBODIMENT
The present invention is a first line emergency response system and apparatus
for pre-hospital or initial in-hospital treatment of patients experiencing an
acute to sub-
acute tlirombotic vascular obstruction and/or associated vessel spasm. The
enzergency
application of high aniplitude, noninvasive, transcutaneously imparted low
frequency
vibration, optimally as a synergistic adjunct to systemically delivered drug
therapy, with
or without concomitant ultrasonic imaginQ, for lysing and vasodilating acute
vascular
thrombotic obstructions, relieving spasm (if associated), and thereby
restoring blood
perfusion is disclosed. The invention is particularly effective against
thromboses in the
thoracic / mediasteinal cavity.
Low frequency vibration shortens the onset and accelerates the effectiveness
of
thrombolytics. Due to the urgency to treat heart attacks, strokes, pulmonary
emboli, or
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WO 2005/023121 PCT/CA2004/001621
acute peripheral arterial obstructions to major vessels, as cell death is
directly
proportional to time, it is of utmost importance to enhance the onset and
accelerate the
effectiveness of the imparted drug treatment in lysing or clearing vascular
obstructions.
The noninvasive application of low frequency vibration, in addition to its
potential
immediate availability to expedite emergency treatment, has the further
advantage of not
causing undue heating of the overlying tissue superficial to the site of
vascular
obstructions. Furthermore, the localized'oiophysical nature of low frequencv
vibration
treatment is advantageous in that as it is not a drug, it will not cause
adverse systemic
biochemical effects, which can otherwise be difficult to reverse such as
hemorrhage.
The term "vibration" according to the present invention relates broadly to a
repetitive back and forth movement of an attachment interface (or vibratory
contact) to
be applied to or strike against (or percuss) a body surface of a patient, and
should not be
construed to mean, or be limited to any particular form of vibration unless
othenvise
specified. Furthermore, the term "continuously applied" or "continuous"
vibration
refers to vibration applied without a substantial break (or pause) in cadence
(i.e. in
accordance with the selected frequency), regardless of the duty factor of the
wave form
emitted. For cardiac applications in particular, "continuous" vibration refers
to vibration
imparted throughout (or substantially throughout) the cardiac cycle, and not
just during
the diastolic or systolic phase of the cardiac cycle.
The preferred embodiment of the emergency response system, or "Vibrinolytic
Therapy", involves the application of continuously applied, noninvasive
mechanical
vibration at a frequency of 1-1000 Hz, preferably 20 - 120 Hz, and oprimally
50 Hz to
the chest wall as an adjunct to thronibolytic therapy in the treatment of
acute myocardial
infarction ("Alvll"). A maximized source output displacement amplitude ranging
from 1
up to 15 mni is selectively provided in the I - 120 Hz range. Displacement
amplitude
control enables the adjustment of vibration intensity to a tolerance level of
a patient,
which will vary markedly depending on the constitution of the individual
treated. The
emergency response system is not complicated and can be applied by a minimally
trained paramedic or nurse without the need for special skilled imaging
guidance or
targeting.
The emergency response system facilitates the action (i.e. enhances the
diffusability and penetrability) of drugs such as: thrombolytics (e.g.
ACTIVASETM
(Alteplase), TNKaseT" (Tenecteplase), RETAVASETm (Reteplase), AbboldnaseTM
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(Urokinase), KabikinaseTM (Streptokinase with water), StreptaseTM
(Streptokinase with
0.9% NaCI solution), and Lanoteplase); GP 2b 3a platelet inhibitors (e.1g.
ReoProT"
(Abciximab), AGGRASTATTM (Tirofiban hydrochloride), and IntegcelinT"
(Eptifibatide)); calcium channel blockers (e.g. ISOPTL~~" SR (Verapaniil HCl).
ADALATTMI~I.T''' (Nifedipine), Cardizem"' (Diltiazem), and NORVASCT"
(Anilodipine besylate)); Nitrates (e.g. Nitroglycerine (spray, pill or patch),
isosorbide
dinitrates (IsordilTM and SorbitrateTM), and NiprideTM (Nitroprusside)); Oral
anti-
platelets (e.g. Acetylsalicylic Acid (Aspirin), Plavi_xTM (Clopidogrel), and
TICLIDTM
(Ticlopidine hydrochloride)); Anti-coagulants (such as heparin, and other
blood thinning
and coronary vasodilatory niedication); concentrated oxvgen and oxygen of
ambient air.
Micro bubble solutions which lower the cavitational threshold of a medium niay
also be
considered as a further adjunct to the above listed pharmacological agents in
conjunction
with vibration therapy. Examples of micro bubble solutions include: EchoGenTM
(Dodecafluoropentane emulsion),=AlbunexTM (5% human albumin), LEVOVISTT"'
(Galactose-Palmitic Acid ultrasound contrast agent), Air containing albuniin
microcapsules (QuantisonTM and MyomapTM), SonoVueTM (Sulfurhexafluoride) and
Perfluorocarbon containing microbubbles (Perfluorocarbon exposed sonicated
dextrose
albumin PESDA). It should be understood that vibration therapy may be used to
facilitate the action of a single drug, or a plurality of any of the
aforementioned drugs in
any combination, according to their preferred use.
The low frequency vibration is imparted to the chest wall (or other
transthoracic
body surface), and tliereby by transmission to the epiniyocardium of the heart
and
coronary arteries. The preferred embodiment (i.e. vibration adjunctive to
thrombol)rtic
therapy) is particularly effective for the treatment of acute ST elevation
myocardial
infarction comprising an acute coronary thronibotic event. Vibration therapy
can, with
drug delivery, also be utilized for other forms of acute coronary syndromes
such as Non
Q wave (i.e. "Non ST elevation") MI or Unstable Angina where symptoms are
otherwise
refractory to medical management. A lower displacement amplitude may be
considered
for Non ST elevation coronary syndromes (e.g. to prevent bruising to the chest
wall),
wherein the displacement amplitude (or in a variation, force) of vibration is
gradually
titrated upwards until a relief of symptoms (or resolution of
electrocardiographic
evidence of ischenlia) is realized.
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Vibrinolytic therapy is effective as a first line medically adjunctive
noninvasive
mechanical intervention to coronary thrombolysis. During cardiogenic shock,
lytic
therapy alone, especially without the inunediate availability of a cardiac
cathlab, has a
low rate of success, yet often remains the only realistic chance for
reperfusion and in-
hospital survival in centers without the option of emergency rescue
Percutaneous
Coronary Intervention ("PCI"). Vibration therapy may also be employed in
conjunction
with a lower dosage of thronibolytic drugs, independently, or in conjunction
with other
forms of medications when thrombolytic therapy is either contraindicated (e.g.
because
of a risk of bleeding), or not prescribed (e.g. non-ST elevation iVI[ or
unstable angina
refractory to conventional medical nianagement).
There are three primary effects of Vibrinolytic Therapy. First, thromboses or
clots are disrupted as the mechanical agitation creates sheer stresses due to
cavitation
and sonic streaming and thereby loosens or breaks apart the clot, resulting in
increased
fibrin binding sites, and improved lytic penetration. Second, sonic streaming
(unidirectional motion of fluid in a vibration field) and convection currents
aid the
diffusion process and promote mixing of intravenous drugs from the systemic
circulation
to the occluded, zero flow culprit vessel. Third, coronary vasodilatation
within the
culprit circulation is achieved as the smooth muscle within the tlirombosed,
often
spasming coronary artery wall is relaxed by vibration (due to a vibration
induced
decoupling of the actin - myosin filaments of the sarcomere). Secondary
tlierapeutic
effects include a localized endogenous release of tissue plasminogen
activator, an
improved left ventricular ("LV") myocardial relaxation with a lowering of LV
diastolic
pressures (and thus potential improvements to diastolic, transmural coronary
flow), the
potential for a positive inotropic effect (leading to an increased lytic
filtration pressure
which is particularly useful in cardiogenic shock cases), the potential for
decreased
myocardial oxygen demand for equal contractility, and an improvement of lung /
gas
oxygen exchange (to provide additional oxygen to the heart and help relieve
ischemic
burden).
Referring to Figure 1, a patient 20 undergoing Vibrinolytic Therapy according
to the preferred embodiment is shown (Ns, drugs, nasal prongs and monitoring
equipment etc. not shown). The preferred engagement nieans, the hands of an
operator,
for applying low-frequency vibration to the patient 20 is shown. Treatment
begins with
the administration of N systemic thrombolytic therapy, plus any other helpful
drug
CA 02540439 2006-01-27
WO 2005/023121 PcT/cA2004/001621
which is designed to effect clot dissolution and/or vasodilate the culprit
coronary vessel.
Thrombolytics may be continuously administered intravenously, and/or by bolus
as
prescribed by the physician. The contacts 12 of the preferred vibrator 10 are
placed at
the treatment site upon the chest wall of the patient 20, and vibration at
high
displacement amplitude (preferably the highest tolerable and judged safe to
patient 20)
is initiated. Vibration is preferably administered once drng therapy has been
established, however may alternatively be initiated before or concurrent with
the
administration of drug therapy.
In acute myocardial infarction cases treated in an Emergency Roon1 preparation
of the patient 20 should include sedation in similar manner to that of a
cardiac cathiab
PCI treatment where the patient is expected to remain flat (preferably supine)
and
relatively still for a period of time despite an anticipated uncomfortable
procedure. The
recommended application time is half an hour to an hour, or until clinical
si=s of
reperfusion become manifest. An intravenous line is established for
introduction of
thrombolytic therapy, and any other IV therapy. Sedatives and anti-nausea
medication
and a foley catheter may be administered to avoid interruptions of treatment.
A
superficial administration of lidocaine to the skin of the chest wall
application site may
be considered. Oxygen should be administered to assist breathing. Intubation
may be
required with congestive heart failure cases in order to maintain oxygen
saturation and
patient positioning in a near supine position. When treatment commences in the
field
(as in an ambulance en route to hospital) a less extravagant preparation may
be
considered, and simply reclining a patient onto a stretcher with the
establishment of an
intravenous line would suffice in most situations.
For use of vibrator 10, the patient 20 is preferably placed supine, altliough
hvo
pillows behind the head may be allowable when the patient 20 is short of
breath.
Referring to Figure 2, a variant means of engagement of vibrator 10 comprising
clanip 100 is shown. The base (not shown) of clamp 100 is placed under the
back or
under the mattress of patient 20. Vertical bar 106 extends substantially
vertically from
the base. Horizontal arm 108 is slide-ably (i.e. in the vertical direction)
and rotatably
(i.e. in the horizontal plane) attached to bar 106 and extends at
substantially 90 degrees
from bar 106, whereby arm 10S will overhang the torso of patient 20.
Horizontal arm
108 is lockable to vertical bar 106 by locking knob 107, or other suitable
means.
Vibrator 10 is attached to arm 108 via slide-able sleeve 116. Sleeve 116 is
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WO 2005/023121 PCT/CA2004/001621
advantageously of a rectangular box shape, and is horizontally slide-able and
disposed in
the horizontal direction along ann 108. Sleeve 116 contains a central,
threaded, vertical
hole defmim, an internal threaded screw column (not shown), with a matching
engatzement screw 110 disposed and attached witlun the screw column. Sleeve
116
furtlier includes locking lmob 109, which tightens to lock vibrator 10 in
place along arm
108. Vibrator 10 is selectively lowered and raised with engagement screw 110,
which
has threads that engage the interior surface of the threaded screw column. The
lower or
active end of engagement screw 110 removably attaches the non-active end of
housing
14 of vibrator 10. Set screw 119 is mounted horizontally through the top
portion of
sleeve 116 and abuts en2agement screw 110 thereby locking it in place during
operation.
A rotatable circular piece 11S disposed at the surface within the non-active
end of
housing 14 is provided such that housing 14 may remain stationary while
engagement
screw 110 adjusts vibrator 10 up or down. Inertial weight 114 is optionally
added to
arm 108 to dampen the movement of arm 108 during treatment. Clamp 100
engagement
is advantageous as it frees an operator to perform other useful tasks.
The shaft 16 of vibrator 10 extends from the lower or active end of housing
14.
A cross-shaped bifurcated connector 13 with a pair of bifurcated support arms
(described later) is remove-ably attached to shaft 16. A pair of contacts 12,
advantageously of silicone rubber, are attached to the support arms of
bifurcated
connector 13, and provide the attachment interface with the patient 20. The
preferred
placement of contacts 12 (i.e. the default placement) is the fourth
intercostal space,
about 2 cm anatomically rightward and leftward to the sternal niargins (i.e.
so the
medial edge of each contact 12 is roughly 2 cm lateral to the sternal
margins).
Alternatively, bifurcated connector 13 is oriented obliquely to the sternum of
the
patient 20 such that the contacts 12 are placed to the anatomic left fourth
intercostal
space and anatomic right fifth intercostal space, or as a further alternate,
the anatomic
left third intercostal space and anatomic right fourth intercostal space in
order to better
localize the source of vibration therapy to the plane of the base of the heart
wherein the
coronary arteries arise from the aorta, and are therein substantially
distributed.
As an alternate for patient 20 positioning, patient 20 may be rolled over into
the
prone position, wherein contacts 12 of the vibrator 10 are placed to bridge
the spine of
patient 20 at the thoracic level. This offers a niuch more comfortable
application to the
patient 20 (which is of special importance in,the case that patient 20 cannot
tolerate high
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intensity concentrated forces to the chest wall), and a higher displacement
amplitude
vibration with a higher engagement force (i.e. force applied by the operator
to vibrator
against the body surface treated - discussed later) may be selected. This
position, as it
is more stable and conifortable to the patient 20, is more particularly suited
to clamp 100
i engagement, which (as stated) advantageously frees the operator.
Referring to Figure 3, the preferred attachment interface according to the
preferred embodiment of bifurcated connector 13 is shown. Bifurcated connector
13 is
comprised of a cross shaped base consisting of a pair of support arnis 22,
with a
substantially columnar support structure 24 oriented at 90 degrees to support
arms 22,
10 and an upper vertical member 15, into which shaft 16 is inserted and is
retained by
means of friction, (or optionally any other known attachment means). Support
structure
24 is not essential, but is preferred to enable the addition of.further paired
support arms
22 (and further contacts 12) at the discretion of an operator (described
later). Bifurcated
connector 13 is removably attached to shaft 16 of vibrator 10. As an option,
bifurcated
connector 13 may be fixed in place to shaft 16 of vibrator 10. The operator
slides
contacts 12 along support arms 22, so as to aceommodate various chest wall
sizes and
sternum sizes. Each contact 12 is attached to sleeve 25 with locking screw 21,
placed
slide-ably and lock-ably upon each support arm 22 of bifurcated connector 13.
Each
sleeve 25 disposes a contact 12, wherein each contact 12 is removable to each
sleeve 25
by a screw mechanism (not shown). Optionally, the spacing between contacts 12
may
be made electronically adjustable by means of an operator adjustment control.
The choice of attachment interface and resultant number of contacts 12
utilized
comprises a risk / benefit decision where the risk is patient bruising and the
benefit is
superior chest wall penetration of vibration thereby improving thrombolysis.
The use of
more contacts 12 will potentially result in relatively more bruising.
In reference to Figure 4, a variant means of chest wall attachment comprises
the
bifurcated connector 13, wherein support structure 24 is utilized to receive a
pair of slide
able sleeves 23, each sleeve 23 comprising an additional pair of support arms
22 to
enable the attachment of up to three pairs of contacts 12 to preferably bridge
the stemum
at the level of multiple intercostal space levels, namely the 3rd, 4th and 5th
intercostal
space. Sleeves 23 are lockable to support structure 24 by lock-ing screws 26.
To even further optimize the treatment, a further contact 12 with sleeve 25
(not
shown) is optionally placed more laterally on at least one of the anatomically
leftward
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oriented support arins 22 at the discretion of an operator, in order to enable
application
to the left mid clavicular line of the patient 20. This particular arrangement
enables
improved penetration to the mid Left Anterior Descending Artery in Acute
Anterior MI.
In further reference to Figure 4. a modified chest wall attachment of
bifurcated
connector 13 (with additional ttvo pairs of support anns 22) may optionally be
utilized to
provide attachment for contacts 12 to the anatomic left 3rd, 4th and 5th
intercostal
spaces along the anatomic left sternal border and anatomic left mid-clavicular
line_ This
is accomplished by simply moving vibrator 10 (and thereby bifurcated connector
13 with
additional two pairs of support arms 22) to the anatomic left of patient 20,
such that the
contacts 12 seat against the left sternal tnargin as well as within the left
mid-clavicular
line (i.e. as opposed to bridging the sternum). This modified chest wall
attachment
optimizes therapy directed specifically to the Left Anterior Descending Artery
("LAD"),
where the diagnosis of acute anterior myocardial infarction has been made and
the LAD,
or any significant, large, leftward, coronary vessel is presumed the culprit.
Alternatively, separate engagement means and a second vibration device (not
shown)
running preferably in phase (i.e. to avoid destructive interference of the
vibratory
signal) with pre-established vibrator 10 (or equivalent), may be utilized to
provide
additional tlierapy along the anatomicai left mid-clavicular line and thercby
the LAD
distribution of the patient 20. It should be noted that vibration therapy may
be
contraindicated to the left 5th intercostal space (and lower intercostal
spaces) at the level
spanning the niid-clavicular line to the lateral margin of the chest wall of
the patient 20
(i.e. approximating the apical window in standard 2D echocardiography), due to
the
remote possibility of intra-ventricular, apical early clot formation. While
intra-
ventricular thrombus formation is not generally considered a significant risk
factor in the
hyper-acute phase of an evolving acute myocardial infarction (i.e. period of
time where
thrombolytics are given), caution is warranted in certain cases. Such cases
include
patients who present "late" and who have the development of significant Q
waves to the
precordium on their initial 121ead ECG. In these cases (and in reference again
to Figure
4) the cotitact 12 of the support arm 22 which is othenvise directed to the
5th intercostal
space of the mid-clavicular line may be removed. Altematively, an expedited 2D
echocardiographic inspection of the apex of the heart of the patient 20 to
rule out early
clot forma.tion (good images supplying apical endocardial resolution in a non-
foreshortened view as judged by an experienced echocardiographer must be
obtained)
24
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA2004101-1621
would identify a low-risk group and thereby vibration therapy to the apex may
connnence as per the judgment of the attending clinician.
As a further option for thoracic cavity placement, (again when high intensity
vibration is not tolerated to the chest wall of the patient 20), bifurcated
connector 13
with additional two pairs of support arms 22 may be placed to bridge the spine
of the
patient 20, at a transverse level equating to approximately the 3rd, 4th and
5th
intercostal space of the anterior chest wall, with the patient 20 reclined in
the prone
position.
In reference to Figure 5, a variant connector 19 comprising upper vertical
member 15 (adapted for removable attaclunent to shaft 16 of the vibrator 10),
and a
variant base consisting of support structure 24 (in isolation) adapted to
receive a pair of
slide-able variant sleeves 27 is shown. Each variant sleeve 27 incorporates a
medially
located semicircular notch, and a pair of support amis 22 to enable the
attachment of
two pairs of contacts 12 in total (i.e. one contact 12 disposed on each
support arm 22).
This configuration enables the bridging of the sternum of the patient 20 via
two pairs of
application sites (i.e. via a total of four contacts 12) at the level of a
pair of nitercostal
space levels, preferably the 3rd and 4th intercostal space. Altematively,
variant
coimector 19 may be placed such as to bridge the sternum at the 4th and 5th,
or 3rd and
5th intercostal space level, and in yet a further variation, variant connector
19 may be
placed obliquely across the sternurri wherein the anatonucally leftward
oriented contacts
12 are placed one intercostal space higher (or superior), to the anatomically
rightvrard
oriented contacts 12 (i.e. such as to match the configuration of the base of
the heart, as
described earlier). The upper vertical member 15 (or optionally any other
known
attachnient means) is disposed centrally and at a right angle to support
structure 24 and
preferably maintained equidistantly between slide able variant sleeves 27 (and
thereby
between the adjacent pair of supports arms 22), in order to enable a balanced
configuration of attaclunent to the patient 20. The spacing between variant
sleeves 27
(and thereby opposing support amis 22 and contacts 12) are slide-ably
adjustable along
support structure 24 (i.e. in a "longitudinal" direction, head to foot
relative to the patient
20), and the spacing between contacts 12 is also adjustable along support arms
22 (i.e. in
a "lateral" direction, side by side with respect to the patient 20).
Optionally, the spacing
between variant sleeves 27 (in the "longitudinal" direction) and contacts 12
(in the
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA2004/001621
"lateral" direction) niay be made electronically adjustable by means of an
operator
adjustment control.
To reduce the risk of bruising, the preferred bifurcated connector 13 giving
rise
to a pair of contacts 12 (as described) may be chosen.
Alternatively, to further minimize the extent of chest wall bruising to the
patient
20, a solitary contact 12, attached to a variant, non-bifurcated connector
(not shown),
may be used. Solitary contact 12 may be located over a solitary target site on
the patient
20 which by default is the 4th intercostal space, with the placement of the
medial edge
of the solitary contact 12 preferably about 2 cm anatomically leftward and
lateral to the
left sternal margin. In a further variation, the solitary contact 12 may be
adapted to be
placed by friction (or any other lmown attachnlent means) directly upon shaft
16 of the
vibrator 10 without the use of yariant, non-bifurcated connector (or other
connecting
means).
This variant technique (i.e. use of solitary contact 12), may be utilized,
regardless of bleeding and or bruising risks, in the special cases of
Anterior, Antero-
Septal, or Antero-Lateral A,lvII, where the leftward coronary circulation is
presunied tlie.
culprit and whereby solitary contact 12 is placed anatomically leftward to the
sternunl of
the patient 20. To improve efficiency and penetration of this variant
teclmique, the
patient 20 may be rotated from the supine position onto his or her left side
(e.g. between
about 20 and 90 degrees from the plane of the bed) and supported for example
by
pillows or a wedge, as this position drops the heart and left coronary
circulation further
leftward from under the sternum bringing the culprit vessels (i.e. the Left
Main, Left
Anterior Descending and Left CircutnIIel) in closer proximity to solitary
contact 12
which has been placed leftward the sternum. In the case of clamp 100
engagement, to
maintain correct orientation and a perpendicular alignment between solitary
contact 12
and the chest wall of the patient 20 (i.e. wherein patient 20 is not l}ring
perfectly supine),
a rotating, pivoting and locking universal joint (not shown) may be
incorporated at the
juncture of the lower aspect of engagement screw 110 and rotatable circular
piece 118 of
the non-active end of housing 14 of the vibrator 10. In these cases the
patient 20 should
preferably be only partially rotated onto his or her left side (i.e. up to
about 20 degrees
from the plane of the bed) such as to maintain structural stability of clanip
100
engagement. Alternatively (and preferably) the hand engagement, or a belt
engagement
(described later) may be utilized.
26
CA 02540439 2006-01-27
WO 20115/023121 PCT/CA2004/001621
Next, the vibrator 10 is turned on, (preferably at a low displacement
amplitude
level such as 2 nun) and the contact or contacts 12 are placed against the
target site (or
sites) on the patient 20.
In an attempt to more exactingly position the contact or contacts 12 in
relation to
the heart, the attending phvsician, nurse or paramedic may first confirm or
optimize a
choice of a single selected intercostal space, chosen from the anatomically
leftward 3rd,
4th or 5th intercostal space, using a stethoscope wherein relative loudness of
heart
sounds suggest anatomical location of the heart, as well as optimal sonic
transmissibility
through the chest wall. The pair of contacts 12 (comprising the preferred
attaclunent
means) should be placed to either side of the sternum, with the anatomically
leftward
oriented contact 12 placed upon the deternuned intercostal space as judged by
the
stethoscope method. The anatomically rightward oriented contact 12 should be
placed
either perpendicularly across the sternum at the level of the chosen "optimal"
intercostal
space, or obliquely across the stemum whereby the anatomic rightward placement
of the
contact 12 is placed one intercostal space lower (or inferior) to the anatomic
leftward
placement of the contact 12. The sternal margin (i.e. so the medial edge of
the contacts
12 are applied directly over the sternal margin) may be considered for large
breasted
women. The heart sounds should be inspected along the anatomic left stemal mar-
gin, so
as to identify the optimal leftward intercostal space. As an altemative means
of
attachment, solitary contact 12 may be placed anatomically leftward to the
stemum at
the determined optimal intercostal space chosen by the operator according to
the
stethoscope method. Relative loudness and sustain ability of heart sounds
during gently
held inspiration should preferably be evaluated by the operator (the louder
the better)
when judging the quality of a sonic treatment window and also inspecting for
heart
location which is known to vary markedly depending on the individual treated.
The
target intercostal space wherein heart sounds are best heard is then marked
with ink (or
crayon, or felt, or any other marker), and the anatomically leftward oriented
(or solitary)
contact 12 of the vibrator 10 is placed in proximity to the mark.
In a filrther alternative method to minimize bruising and to establish optimal
transmission to the heart, vibration therapy may be provided in conjunction
with high
frequency, diagnostic ultrasonography (i.e. "HFUS" around 1- 7 IvIHz), in
order to
optimize placement of the contact or contacts 12 of the vibrator 10 to the
chest wall of
the patient 20. To confirm the ideal placement of the low frequency treatment
vibration
27
CA 02540439 2006-01-27
WO 20051023121 PCT/CA200-1/001621
source; a trained HFUS operator (such as a Cardiac Ultrasound Technologist, or
echo
trained Cardiologist for example) must first locate the ideal parastemal sonic
penetration
window via ultrasonographic techniques, wherein the preferred sonic window
provides a
clear visualization of the mid to basal aspect of the heart, (ideally
depicting the basal
aspect of the akinetic or hypo kinetic myocardial wall which represents by
anatomic
reference where the culprit thrombus is most likely to reside). The imaging
probe is
preferably maintained in a near perpendicular orientation relative to the
surface of the
chest wall interrogated. The attachment variation comprising solitary contact
12 is
preferable in these cases to minimize overall chest wall trauma, and focus the
intensity
of the therapeutic vibration over the optimized placement site comprising the
determined
sonic penetration window. Optionally the ottierwise preferred pair of contacts
12 may
be placed to either side of the sternum, with the anatomically leftward
oriented contact
12 placed upon the determined sonic penetration window, and the opposing
anatomically rightward contact 12 placed either perpendicularly across the
sternum at
the same intercostal space level, or one intercostal space lower (or inferior)
to the
leftward oriented contact 12. The operator employs a conventional two-
dimensional
ultrasound device (not shown), so as to mark the determined sonic penetration
window
on the chest (e.g. with a pen or felt inarker) and place and optionally an-le
the chosen
attachnient interface of the treatment vibrator 10 accordingly. As stated the
sonographer
should preferably (while imaging) hold the imaging probe substantially
perpendicular to
the chest surface (i.e. ideallv less than a 20 to 30 degree angulation from
the normal to
the chest wall) such as to ensure a sonic penetration window which is
prosinZate the
target area, and which is also consistent with an anticipated perpendicular,
or near
perpendicular attachment of the contact or contacts 1' of the low frequency
treatment
vibrator 10. Pathologies such as COPD, with increased lung size and therefore
interference with ultrasound, may indicate the use of different intercostal
spaces (i.e_
such as the 5th intercostal space) to establish the optimal sonic penetration
window.
Attachment means can be by hand, clamp 100 or a variety of engagement garments
(which are described later). The parastemal chest wall is preferred but otlier
sonic
windows may be utilized (note that the apical window should be used
judiciously as per
the nzethodology as stated earlier).
In a further variation of the above HFUS imaging method, a "dual function",
simultaneous vibration and imaging system may be employed via a single
combined
28
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA2004/001621
imaging / treatment probe (described in detail later). In this variation to
the preferred
embodiment, low frequency vibration therapy is advantageously employed in
conjunction with high frequency ultrasonography (i.e. HFUS), where both high
and low
frequency wave forms are applied simultaneouslv (i.e. in real time) via a
single
instrument, which comprises an ultrasonic imaging transducer operatively
connected (or
acoustically coupled) to the active end of a low frequency vibration source
operational
in the 1- 1000 Hz range. The ultrasound imaging transducer acts in this case
as a
variant attachment interface (or contact) to the patient 20, thereby enabling
the
transmission of low frequency vibration from the vibration source, while
concurrently
enabling ultrasonic inlaging to direct vibration, at the discretion of an
operator. The
method of the dual function system comprises the placement-of the imaging /
treatment
probe (with the accompaniment of ultrasonic conduction gel) to the skin of the
patient
20, such as to establish a sonic penetration window depicting a target of low
frequency
vibration (such as the base of heart in A1Vf[ cases, as described earlier).
Once a sonic
penetration window is established, low frequency vibration is initiated and
transmitted
through the ultrasound imaging transducer attachment interface (preferably as
an adjunct
to drug therapy), and the application site is additionally maintained through
continued
monitoring of the ultrasonic image provided. In this manner, intelligible
anatomic
placement and angulation of the imaging / treatment probe is achieved, thereby
optimizing the delivery of low frequency vibration therapy to the culprit
vascular region
targeted.
Optimally in still a further variation, low frequency ultrasonic treatment
(LFUS)
is also used in combination with HFUS imaging and low frequency treatment
vibration
in the 1- 1000 Hz range, via a "multifunction system" employing a single
variant LFUS
enabled imaging / treatment probe (not shown and described later). In this
variation to
the preferred embodiment, low frequency vibration therapy is en-ployed in
conjunction
with high frequency ultrasonography (i.e. HFUS) and "treatment" low frequency
ultrasound (i.e. LFUS) simultaneously and in real time, where all three wave
forms are
applied in concert via a single transmission instrument. In this manner,
direct HFUS
imaging and targeting may be combined with low frequency vibration in the 1-
1000 Hz
range, and low frequency ultrasonic energy (at around 20 - 100 kHz, preferably
27 kHz),
to optimally agitate and disrupt the culprit vascular region targeted.
29
CA 02540439 2006-01-27
WO 21105/023121 PCT/CA2004/001621
The use of a combined imaging / treatment probe, (or "single transmission
instrument"), regardless of employment of the "dual function" or
"multifunction"
system, at least initially involves a skilled imaging technique to direct
vibration therapy
to the ideal sonic penetration window. The use of both hands to support and
maintain
the imaging / treatment probe with enough engagement force to the chest wall
(or other
body part) is suggested, or the operator can altematively, use one hand, or
utilize anv of
the suggested engagement means according to the present invention, as long as
the
appropriate sonic penetration window is visually monitored and maintained. An
inertial
weight may be placed to the backside (or optionally within the housing) of the
chosen
"transmission instrument" adding inertia to the apparatus and therebyassisting
the
operator ergonomically who may hold the transmission instrument in position by
hand.
While the supine position for the patient is generally preferred, different
patient
positioning (e.g. with the patient lying to some degree on his or her left
side, up to the
left lateral debecutis position) could be utilized as per the judgment of the
operator, in
order to establish the highest quality and most stable sonic penetration
window
available. The parasternal windows remain the preferred application site if
available (i.e.
in coronary applications), however other sonic windows may be considered (note
that
the apical window sliould be used judiciously as per the methodology as stated
above).
Duty factor and intensity level may be selected with respect to the LFUS
application (i.e.
in the multifunction system), such as to provide the means to avoid undue
heating to the
skin surface of the patient 20. Alternatively, a wet cool cloth applied
intermittently to
the slan surface, and/or a periodic change of application site (or even
transmission
instrument), may be utilized to prevent skin burning of the patient 20 during
joint LFUS
use.
The next step in the preferred treatment method is to apply appropriate
engagement force to the chest wall of the patient 20 with the vibrator 10. The
attending
clinician applies force to the vibrator 10 against the target area by hand, or
altematively
via rotation of engagement screw 110 of clamp 100. A relatively constant, firm
engagement force of at least 5-10 N, preferably 20 - 100 N, and optimally 50 -
100 N.
(measurable at shaft 16 of the vibrator 10 durin, operation), should be
obtained
according to the tolerance and safety of the patient 20. In the case of clamp
100
engagement, engagement force should preferably be first established during
gentle held
expiration of the patient 20. The engagement force should preferably not
exceed 100 N,
CA 02540439 2006-01-27
WO 21111-5/023121 PCT/CA2004/0111621
such as to avoid possible dampening of oscillations of the vibrator 10. A
force meter
(discussed later and not shown) is optionally utilized to confirm engagement
force. For
clamp 100 engagement, the placement of the base of clamp 100 (described later)
under
the mattress of the patient 20, mav be advantageous in some cases, in that the
mattress
provides for a slight decompression when the patient 20 inhales, so as to
limit the
nlaximum engagement force on inspiration and make for a more comfortable
application
to the patient 20. In the preferred case where the vibrator 10 is engaged by
the hand or
hands of an operator, the engagement force can be monitored and niaintained at
a near
constant level, as well as modulated as per the needs (or tolerance levels) of
the patient
20. Referring back to Figure 1, housing, 14 of the vibrator 10 is
advantageously "L"
shaped, incorporating a handle to facilitate hand held operation. Activation
of the
vibrator 10 preferably precedes engagement, however alternatively the vibrator
10 may
be activated after engagement to the patient 20, at the discretion of an
operator.
As a rule of thumb, the engagement force should be the maximum force, which
is tolerable for the patient 20, and will not cause the vibrator 10 to
significantly dampen
(or stop) its oscillations. Satisfactory engagement is filrther identified
once the patient
identifies a "fluttering" in the teeth or jaw (or exhibits an undulation in
the voice)
which indicates efficient transmission. It should be noted that patient
conzfort can be
greatly improved by moving the application sites about, even slightly within
the rib
20 spaces, or alternatively to differing nb spaces (in keeping to the
selection of methods
previously described). Once engaged satisfactorily (i.e. in the case of clamp
100
engagement), the operator tightens set-screw 119 to lock engagement screw 110
in place.
Vibration therapy preferably conunences with selection of the maximum
displacement amplitude or force judged safe and tolerable applied for
emergency
situations. This maximal setting, may result in bruising to the chest wall (or
other body
surface treated), and an infomled consent should preferably be signed by the
patient 20
if feasible.
It should be understood that the exact order (or selection of steps) in the
application of engagement force vs. displacement amplitude level of the
vibrator 10
against the body surface of the patient 20 is not critical, as long as the end
result (i.e. for
vibration therapy) is that a firm engagement force (i.e. at least 5 - 10 N,
and preferably
within the range of 20 - 100 N) at a high displacement amplitude (i.e. greater
than 2 mni,
31
CA 02540439 2006-01-27
WO 200-5/023121 PCT/CA2004/001621
and preferably in the range of at least 4 - 15 nun, and ideally maximized to
patient 20
tolerance) is ultimately established.
If displacement amplitudes of less than or equal to about 2 nun, and / or
engagement forces of less than approximately 10 N are not tolerated to the
chest wall of
the patient 20 (even in the special case where lidocaine is administered to
the chest wall
surface), then patient 20 may optionally be placed in the prone position (not
shown) and
the contacts 12 may be placed to bridge the spine of patient 20 in the upper
thoracic
region. Vibration at higher displacement amplitudes (often tolerable to about
15 mm),
and higher engagenient forces (often tolerable to 100 N or greater), may be
safely
utilized in the majority of these cases, to ensure and masimize penetration to
the
mediasteinal cavity and enhance clinical effectiveness of vibration.
Tests by the applicant have shown that low frequency vibration penetration
through soft tissue is related to the applied displacement amplitude and
engagement
force of the vibration contact to the body surface vibrated. It has been
ascertained that
the desired engagement force of a vibration source placed against the chest
wall of the
patient 20 is preferably at least 5 - 10 N, and optimally greater than 20 N,
and up to 100
N (when tolerated), to confer ideal penetration. When vibration is applied to
the muscle
groups adjacent to the spine of the patient 20 (as an altemative means of
transthoracic
vibration to the mediasteinal cavity), optimal engagement force is much
higlter (i.e.
greater than 100 N may be utilized), as the application is far better
tolerated by the
patient 20, and higher engagement force and displacement amplitudes are
generally
required to achieve therapeutic levels of mediasteinal cavity penetration.
Optimal
displacement aniplitudes also vary significantly with the constitution and
tolerance
levels of the patient 20, as well as the selected body surface treated.
Vibration
displacement anplitudes of greater than 2 mm (and preferably in the range of
at least
about 4 mm - 12 mm), are preferred for chest wall applications, and
displacement
amplitudes of at least about 6 nun - 15 mm are preferred for transthoracic
applications
from the backside of the patient 20. In the case where ultrasonic (HFUS)
imaging is
employed to direct or target vibration therapy, penetration to the heart is
generally
increased, and higher amplitudes and engagement forces of vibration (i.e.
which may
cause bruising to the skin surface vibrated and patient 20 discomfort) are not
absolutely
required. Still however (regardless of the use of HFUS enabled directed
therapy), the
highest possible combination of engagement force and displacement amplitude is
still
32
CA 02540439 2006-01-27
WO 20115/023121 PCT/CA2004/0111621
recommended to yield best results in emergency treatment of acute thrombotic
vascular
obstructions.
In the case that the patient 20 is unable to tolerate even modest levels of
vibration (i.e. both displacement amplitude and engagement force, regardless
of body
surface vibrated), then a gentle application utilizing the weight of the
vibrator 10 (or at
the least 5 newtons of engagement force) and the maximum low level of
displacement
amplitude tolerable to patient 20 should be utilized. Displacenient amplitudes
of 1- 2
mm (or even less, e.g. 0.1 - 1.0 mm - accomplished through dampening vibration
through a cushion for example) may be used in these cases.
The frequency range employed is between 1-1000 Hz, preferably between 20 -
120 Hz, and optimally 50 Hz. It is preferable to match the resonance frequency
of the
heart, which falls within a 20 - 120 Hz range. The heart, receiving vibration
stimulus at
or near its resonance frequency will vibrate with the highest possible
displacement
amplitudes at the localized areas which best receive the signal. External
vibration at the
resonance frequency enables transmission of the vibration signal internally
throughout
the ventricular chambers with highest efficiency, thereby vibrating the entire
heart and
effecting optimal intra ventricular transmissibility. Optinial intra
ventricular
transniissibility aids agitation of the entire coronary tree, including those
parts of the tree
hidden behind lung or soft tissue which are poor transmitters of vibration and
therefore
otherwise difficult to penetrate directly with sonic mechanical energy. The
preferred
frequency for chest wall vibration is a 50 Hz sinusoidal compressional wave,
owing to
this wave-fotms known superior chest wall penetration, intra-ventricular
transmissibility,
lytic penetration, clot disruption, and arterial vasodilatation
characteristics.
Higher frequencies (i.e. 150 -1000 Hz), or even in the sub-ultrasonic to
ultrasonic range (i.e. 1000 Hz -100 kHz), while optional for clot disruption
and improved
drug action to sites of thromboses, are generally higher than the resonance
frequency of
the heart and hence not readily transmissible to all areas of the coronary
anatomy bv
intra ventricular transverse transmission nieans. Higher frequency vibration
also
requires diminished displacement amplitude for safe clinical use, which is a
further
limitation to this wave-form's potential penetrating and agitative power (i.e.
through the
chest wall or other body part treated). A directed approach through an
identifiable sonic
penetration window to ensure adequate penetration to target areas by the much
weaker
(i.e. lower displacement amplitude - in the low millimeter to sub millinieter
ranges)
33
CA 02540439 2006-01-27
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signal is strongly recommended for frequencies greater than 150 Hz, again at
the highest
amplitudes and forces judged tolerable to a patient in emergency situations.
Concomitant simultaneous high frequency ultrasound imaging (i.e. HFUS) in
conjunction with lower displacement amplitude vibration therapy at frequencies
of
greater than 150 Hz, to target and direct a sonic penetration pathway to
culprit areas (as
per the dual function system described earlier), is the optimal method of
employment for
such higher vibration treatment frequencies.
Generally, a range of frequencies selectively chosen between 1- 1000 Hz, with
the selection of multiple displacement wave-forms is disclosed. The present
invention
provides a broad range of frequencies and wave-forms which are advantageous,
as the
apparatus and system is optionally employed both as a treatment system and a
research
tool.
Treatment continues during and / or post the administration of preferred drug
agent(s) wherein stated agents may be selected solely or in any combination
from the
group of thrombolytics, GP 2b 3a platelet inhibitors, anticoagulants, oral
anti-platelets,
vasodilators, cavitating micro bubble solutions, concentrated oxygen, and the
oxygen of
ambient air. Vibration treatnient ends once clinical signs of reperfusion are
identified or
until emergency invasive treatnient (i.e. PCI and/or emergency
revascularization
surgery) is established.
The preferred vibration apparatus for deliverance of vibration therapy is
represented diagrammatically in Figure 6, where an operator (not shown)
provides input
to processor 34 via interface 50 of the preferred vibrator 10. Interface 50
comprises a
set of manually operated control switches (not sho-ivn), advantageously
located for easy
access on the exterior surface of housing 14 of vibrator 10. Processor 34 in
turn controls
vibrator 10, delivering the prescribed frequency, displacement amplitude and
displacement wave form (described later) of continuously applied vibration to
the target
site (or sites) on the patient 20 via a sole attachment interface. As an
option to interface
50, other variant interfacing means such as an electronic touch pad or Icey
board (either
located remote or on housing 14) may alternatively be employed. Processor 34
is
advantageously located within housing 14 of vibrator 10, and comprises a
programmable
logic control of imown type. The preferred vibrator 10 is pariicularly
appropriate for
first line treatment such as in emergency rooms and ambulances during
transport, where
in both cases non-experts are operating the device. The preferred embodiment
is
34
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA2004/001621
designed to provide a simple and reliable first line response to A.~II
incidents, which can
be operated with minimal training and easily applied in the field or emergency
room
setting.
Referrine now to Figure ?, in some cases it may be preferable to apply
vibration
therapy with an "advanced method" comprising use of physiological and
mechanical
monitoring or sensing equipment and varying timing and / or frequency
algorithms for
vibration delivery. With varying algorithms, cardiac phase dependent time and
optionally frequency varied vibration therapy may be employed when best suited
to the
clinical situation. Enablement of the "advanced method" is provided via a
variant
cardiac pliase controlled vibrator 11 (i.e. "variant 1"), which is
advantaQeously of like
construction to preferred vibrator 10, but is adapted to receive and respond
to more
advanced commands from variant processor 35 and a variant interface 51. In
this
variation, both variant processor 35 and variant interface 51 are located
remote from the
housing of variant cardiac phase controlled vibrator 11.
The needs for varying timing and frequency algorithms in vibration therapy
will
differ depending on the clinical presentation. For example, in cases of
hemodynamically
stable acute ST elevation myocardial infarction, continuous vibration which is
cardiac
phase controlled whereby approximately 50 Hz vibration is inlparted durinQ
ventricular
diastole and approximately 100 Hz during ventricular systole may be employed,
which is
suspected by the applicant of the present invention to produce a more
therapeutic result.
Any known phase monitoring means (see below) may be used to determine the
tiniing of
the cardiac phase, and this is firstly determined automatically via variant
processor 35,
and then is optionally further fine-tuned by an operator via an adjustment (or
"vibratory
timing adjustment control") made to variant interface 51. Cases of
complicating
cardiogenic shock or unmanageable congestive heart failure with acute ST
elevation
myocardial infarction dictate diastolic only timed vibration. Vibration timed
specifically
to the diastolic phase of the cardiac cycle provides a form of ventricular
assist with a
positive inotropic effect, and, as the diastolic mvocardiuni is particularly
stiff in times of
profound ischenua, the vibration signal exhibits excellent intra ventricular
transmissibility (i.e. transversely propagated intemal vibration) to ensure an
agitative
treatment response to all areas of the coronary circulation. It is significant
that the
conventional treatment of acute yII with the complication of cardiogenic shock
with
thrombolytics only (i.e. with no adjunctive interventional or mechanical
treatment) is
CA 02540439 2008-06-02
WO 2005/023121 PCT/CA2004/001621
extremely ineffective, with a low likelihood of repertusion and a 63% in-house
mortality
reported.
In the advanced method, additional physiological monitoring equipment is
provided
to make possible the application of special vibration timing algorithms
according to cardiac
phase. Such physiological monitors include; electrocardiogram ("ECG") 36,
impedance
plethysmograph 40 (optional), phonocardiography system 42 (optional), and
noninvasive
blood pressure apparatus 44 (optional). The monitoring and sensing equipment,
all of
commercially 7.known types, are interfaced with the patient 20.
A transesophageal accelerometer 38 placed on a transesophageal lead may be
used,
(as disclosed in Japanese Pat. No. JP 4156823 to Takishima et al)., to confirm
and monitor
maximal sonic penetration to the esophagus, which represents the posterior
aspect of the
heart. An external accelerometer 39 is also provided, which is advantageously
placed on shaft
17 of variant cardiac phase controlled vibrator 11 ("variant I"), to assist in
monitoring the
timing of vibration therapy in real time, and to confirm the functioning (i.
e. frequency and
amplitude) of the applied vibration. Alternatively, variant processor 35 may
optionally emit a
signal indicating when variant cardiac phase controlled vibrator 11 ("variant
1") is active. The
nionitored physiological and mechanical output interfaces with variant
processor 35, which is
thereafter processed and sent to display monitor 52 for real time wave form
display. The
operator, based on the output displayed on display monitor 52, may select and
modulate
programmed timing and frequency algorithms designed to optimize therapy by
entering a
selection to variant interface 51 which interfaces with the operator and sends
commands to
variant processor 35.
For example (as mentioned previously), specifically timed sinusoidal cardiac
phase
controlled vibration at 50 Hz in ventricular diastole and 100 Hz in
ventricular systole, at
maximum tolerable force or displacement amplitude, is preferred for use with
the advanced
tnethod in the treatment of hemodynamically stable ST elevation infarcts.
Vibration timed
exclusively to the diastolic phase of the cardiac cycle at 50 Hz (known to
produce a positive
inotropic effect), is preferred for hemodynamically unstable ST elevation
infarcts, (e. g. with
associated cardiogenic shock). ECG 36 output is essential to provide a timing
differentiation
means between the diastolic and systolic phase of the cardiac cycle. Variant
processor 35 will
interpret the QRS deflection as the onset of systole, and will assign a
preprogrammed default
rate related time delay to dictate the timing of the onset of diastole. The
default time delay
36
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA2004/001621
may be monitored and adjusted by the operator (i.e. with the vibratory timirtg
adjustment
control), based on physiological signals viewed upon display monitor 52.
Monitoring
ECG 36 output can additionally provide information to heart rhythm and
reperfusion
which is represented by a sudden decrease in ST segment elevation.
Display monitor 52 comprises a CRT (or other) monitoring screen enabling real
time output wave form display, and digital read outs plus annotations where
all
necessary information for an operator to make judgments is displayed. Variant
interface
51, comprises a combination of an electronic control touch screen and a
keyboard entry
(although other known interfaces such as voice recognition, push buttons,
sliding
switches, control knobs or any other suitable interface may be used), to allow
for
selection and modification of: vibration displacement amplitude, displacement
amplitude according to cardiac phase, displacement wave form selection, ECG 36
monitoring selection, low pass ECG filter (on/off), mode selection (i.e.
diastolic vs.
continuous vibration emission), vibratory timing adjustment control, and
frequency
algorithms. Variant processor 35 is adapted to receive and process input from
variant
interface 51, and through analysis of the physiological information delivered
from the
monitoring equipment, control variant cardiac phase controlled vibrator 11
("variant 1")
to cause vibration at the time period, frequency, displacement aniplitude and
wave form,
as selected by the operator. ECG 36 employs a standard monitoring system to
represent
inferior (II, III, avF), anterior (V lead) and lateral (V5, I, aVL)
electrocardiographic
information, but may be of other configurations. Inipedance plethysmograph 40
comprises a commercially krtown impedance plethysmography system enabling a
relative comparison of real time changes in intra thoracic blood pressure.
Impedance
plethysmograph 40 further relays the timing of the dichrotic notch (signifying
the onset
of diastole) to display monitor 52 and thereby to the operator, making manual
adjustments to the timing of the onset of diastolic vibration more accurate
(however in
the absence of impedance plethysmograph 40, the onset of diastole may be
judged at the
termination of the T wave of the wave form displaved from the ECG 36). The
termination of diastolic vibration is triggered automatically by variant
processor 35 in
recognition of the deflection of the QRS complex provided by ECG 36 monitoring
means. It is therefore important to achieve a good "tall" QRS complex on the
chosen
ECG 36 monitoring lead without a great deal of muscle artifact. A low pass ECG
36
filter (filter not shown), operational with a 40 Hz cutoff is included to
minimize such
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CA 02540439 2006-01-27
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artifact. A wedge filter (automatically set to the frequency of the vibratory
signal) is
also included, to substantially eliminate vibratory artifact on the ECG 36
waveform
trace. Phonocardiography system 42 of known type is optionally included as it
also
provides information as to the timing of the onset of diastole (i_e. by the
initial
deflection of the "S2" heart sound), and thereby provides additional
information to assist
in the nianual adjushnent for diastolic only vibration.
Noninvasive blood pressure apparatus 44 comprises a noninvasive real time
blood pressure monitor provided by arterial tononietry which non-invasively
senses the
pressure of the radial artery by way of an external pressure transducer to
provide a real
time arterial blood pressure wave form, but may alternatively be a noninvasive
blood
pressure monitor of any commercially known type, wliich quantifies the blood
pressure
of the patient 20. For example an automatic noninvasive blood pressure cuff
system
could be utilized with periodic digital readouts sent to variant processor 35
and thereby
to display monitor 52. An electronic strain gauge force meter (not shown) is
optionally
employed to monitor the engagement force of the variant cardiac phase
controlled
vibrator 11 ("variant 1") to the chest wall (or thora.t) of the patient 20.
Alternatively,
any conunercially known gauge such as a weight scale may be used to detemline
the
engagement force. Accelerometer 39, placed on the shaft 17 of variant cardiac
phase
controlled vibrator 11 ("variant 1") is utilized to confirm that appropriate
vibration is
being applied, and to provide a real time comparison of treatment vibration
application
versus ECG 36 and optionally impedance plethysmograph 40, and / or
phonocardiography system 42 wave form trace.
Regardless of method employed (i.e. "siniple" or "advanced"), the patient 20
should preferably be monitored by at least one clinician or nurse during the
course of
vibration tlierapy for treatinent of acute ST elevation niyocardial
infarction. Pain and
nausea may require an adjustment in the anlplitude or engagement force of
vibration or
even a cessation of treatment. The operator can readily adjust or remove the
vibrator 10
(or provided variant) as required. Particularly using the "advanced method",
the
operator or clinician may adjust the treatment to suit patient 20
physiological status
which is displayed on display monitor 52. For instance a sudden drop in blood
pressure,
usually indicating deterioration into cardiogenic shock, would be registered
by
plethysmograph 40 and /or noninvasive blood pressure apparatus 44. The
operator may
decide to discontinue continuous vibration therapy (i.e. vibration applied
throughout the
38
CA 02540439 2006-01-27
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cardiac cycle), which may have a negative inotropic effect on heart failure,
and switch to
diastolic only vibration, which is known to provide a positive inotropic
effect. If
hemodynamic compromise is borderline, the operator may optionally linut or
reduce the
displacement amplitude of vibration selectively during the time period of
ventricular
systole, wliile maintaining maximized displacement amplitude during
ventricular
diastole.
In reference to Figure 8, low frequency vibration via a plurality of
displacement
wave forms with "displacement" on the vertical axis and "time" on the
horizontal axis,
(with respect to the movement of a contact 12) is shown. While the preferred
emboditnent incorporates use of a sinusoidal vibration displacement wave fomi
<a>,
other displacement wave forms of vibration may altematively be selected such
as;
square waves <b> (or "pulsed" or "percussive" waves, with a steep displacement
rise),
saw tooth waves <c> (with a gradual displacement rise), exponential waves <d>
(with
an acceletory, non-linear displacenient rise) or any other linear or nonlinear
wave shape
(or combinations thereof) according to the invention. High impact square wave
<b>
vibration may be particularly advantageous in some instances due to its known
superior
penetration and disruptive characteristics through human tissue.
The above methods of low frequency vibration therapy may be used for several
pathologies and in different settings. Six prophetic examples of clinical use
illustrated
in reference to the heart, in various in hospital or pre-hospital settings are
as follows:
First, vibration therapy may be employed in an emergency rooni or ambulance in
the first line treatment of acute ST elevation myocardial infarction,
preferably adjunctive
to thronibolytics, or any other form of medical therapy.
Second, also in an emergency room or ambulance as a first line treatment,
vibration therapy may be employed to reduce the dosage of thrombolytics and /
or anti-
platelet agents required for those patients where thrombolytic tlierapy and /
or anti-
platelet therapy is relatively contraindicated due to increased bleeding risks
(and also to
save costs), or even eliminate the use of drug therapy entirely.
Third, vibration therapy may be eniployed in the in-hospital or pre-hospital
setting for treatment of chest pain refractory to medical management in cases
of Non-
ST elevation MI or cardiac ischemia preferably as an adjunct to drugs such as
but not
restricted to IV or SL nitroglycerin, GP 2b-3a platelet inhibitors, and
heparin. Lytics are
not indicated in such cases. Gently applied vibration timed to the diastolic
phase of the
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CA 02540439 2008-06-02
WO 2005/023121 PCT/CA2004/001621
cardiac cycle (i.e. via the "advanced niethod"), which is known to increase
coronary flow in
stable, ischemic, non occlusive states (as per the teachings of JP 8089549 to
Koiwa et al) may
be tried in these cases as a first measure to limit vibration therapy and
thereby limit potential
bruising to the patient 20 who may be anti coagulated. The intensity level of
the applied
vibration may be gradually (or incrementally) increased to a threshold of
patient comfort. If
diastolic only vibration does not relieve the chest pain (or if not available)
continuously
applied vibration (i. e. throughout the cardiac cycle, in systole and
diastole) should be
selected, which is more effective for more serious coronary syndromes wherein
the
mechanisms are either or both of coronary artery spasm and coronary thromboses
fonnation.
Continuous vibration should preferably be applied at incrementally increasing
displacement
amplitudes (or force) until the maximal levels of comfort and safety are
realized and the
symptotns are relieved. This gentle method of progression of phase tnodulation
and
displacement atnplitude in ischemic but substantially non-infarcting syndromes
is important
as the situation is not acute, and the patient will likely be (as previously
stated) anti-
coagulated and will bruise easily.
Fourth, vibration therapy niay be employed prophylactically in the step down
teleinetry unit or CCU for example, adjunctive to nitrates (andlor blood
thinning
medications) for more pronounced coronary events (i.e. with ST/T wave changes
on the
ECG telemetry rnonitor) which are otherwise refractory to conventional drug
management,
whereby an acute denovo blood clot and/or acute coronary vessel spasrn at the
earliest of
stages may be in the process of formation. Newly formed (or forming) blood
clots are easily
disrupted and mobilized prior to the deposition of fibrin by the vibration
methods disclosed.
Fifth, vibration therapy may be applied to the chest wall in the cardiac
cathlab setting
as an adjunct to drugs such as nitroglycerine, nipride, verapamil, GP 2b 3a
platelet inhibitors,
and thronibolytics, for acute to sub-acute procedures prior to, during, or
after PCI (or heart
catheterization), where there may be significant clotting in the artery at the
onset of or
innnediately following the procedure. Vibration therapy could for example be
utilized pre-
procedure, as an adjunct to GP 29 2b3a platelet inhibitors +/- thrombolytics
while the patient
20 is en route to the cathlab for emergency PCI. Post procedure, vibration
therapy may for
example be appropriate in "no -reflow" or "slow-flow" situations following or
during an
intervention, for instance when clots and/or
CA 02540439 2006-01-27
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micro emboli dislodge and affix themselves to the distal, arteriolar
circulation to cause
very poor flow, chest pain and injury. It should be noted that if chest wall
vibration
therapy where to be imparted during a heart catheterization (or PCI
procedure), the
guide or diaanostic catheter should be withdrawn from the ostia of the
selected coronary
artery prior to initiation of the vibration therapy in order to avoid shear
forces and
possible dissection to the ostia of the coronary.
Sixth, vibration therapy may be employed in the community for acute states of
coronary insufficiency resulting in symptoms of possible acute myocardial
infarction
refractory to nitroglycerine treatment in the patient 20. Every bout of
"angina" that
patient 20 in the community experiences might represent an acute coronary
event
wherein a plaque has ruptured and a blood clot (and / or vessel spasm) has
formed. In
these cases, patient 20 will typically have tried nitro spray x 3, each dose
spread five
minutes apart, without relief of chest pain which may be quite severe. Patient
20 will
then proceed to dial "911" for emergency assistance, wherein the diagnosis of
an acute
coronary obstruction leading to an acute MI cannot be ruled out until
professional care
arrives. As stated above, hyper acute early clot formation is particularly
amenable to
dissolution via mechanical agitation. High amplitude vibration therapy
concentrated to
the chest wall in these instances can provide such aQitation, and can be
therefore
(prospectively) an extremely important first line emergency tool, for
capturing the
window of susceptibility of a newly formed blood clot and eradicate it before
it has a
chance to grow and harden, and cause damage to the myocardium, or even sudden
death
to the patient 20. For treatment, the patient 20 should be ideally resting in
either the
supine position or seated conifortably upright in a chair. Ideally a friend or
bystander
should provide vibration therapy to the patient 20 (preferably with the
continued
administration of nitrates) until symptoms have dissipated or until
professional care
arrives.
Vibration therapy is effective in emergency situations where an acute vascular
obstruction has occurred and cell death or hemodynamic compromise is imnunent,
particularly when there is a poor prognosis for dru-, therapy alone and
emergency
invasive intervention is delayed or not available.
Acute pulmonary emboli and in particular saddle emboli (which involves a
critical life and death situation) are also good candidates for external,
transcutaneous
vibration therapy adjunctive to standard drug therapy (e.g. N thrombolytics,
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CA 02540439 2006-01-27
WO 200-55/023121 PCT/CA2004/001621
anticoagulants etc.). Chest wall vibration to the vascular region of the lung
(pulmonary
vasculature) and pulmonary artery are readily achieved by the methods
disclosed below.
The underperfused body region in this case is the orszan and tissues of the
lung and, in
the case of saddle emboli, the entire body. A frequency of less than 1000 Hz,
and
preferably selected from the 1- 120 Hz range at maximum tolerable force or
displacement amplitude is suitable for such applications. The choice of 50 Hz
sinusoidal
vibration is preferred, as 50 Hz sinusoidal vibration can be delivered at
relatively hirlt
amplitude, has excellent chest wall to thoracic cavity penetrability, and is
also a well
established frequency known to produce cavitation and acoustic streaming (to
assist in
thrombolytic to clot filtration), as well as vascular dilation and clot
disruption. As an
optiori, square wave <b> (i.e. witli a steep displacement rise for better
penetration and
disruptive action), saw tooth wave <c>, exponential wave <d>, or any linear or
nonlinear (or combination thereof) displacement wave form, may be used (see
Figure S).
As the lungs also reside in the thoracic cavity, the present invention also
functions to
15. vibrate the vasculature of the lungs and pulmonary artery with low
frequency vibration.
Lltrasonic imagin- means to target the pulmonary artery (i.e. where saddle
embolus is
presumed the culprit) may be employed to target the vibration therapy.
Witliout
ultrasonic imagina. the preferred vibrator 10 (with preferably a pair of
contacts 12) is
preferably placed to bridge the sternum at the level of the third intercostal
space of the
patient 20 (which approximates the bifurcation point of the left and right
pulmonary
artery). Alternatively, chest wall attachment may comprise a plurality of
contacts 12
either bridging the stetnum or applied to the left sternal margin of
preferably the third,
fourth and fifth intercostal space. A frequency of less than 1000 Hz,
preferably 1- 120
Hz and optimally about 50 Hz is then applied at maximum tolerable amplitude in
conjunction with a systemically delivered drug such as a thrombolytic, anti-
platelet,
anticoagulant or vasodilatory drug. The application of high amplitude low
frequency
vibration commences adjunctively to drug therapy until signs of reperfusion or
until
invasive corrective measures may be established. Optionally, vibration therapy
may be
utilized independently (i.e. without a drug), or with a decreased dosage of
drugs.
Vibration therapy may also be employed to treat acute Cerebral Vasculature
Accidents, preferably once detetmined as ischemic or embolic in origin,
adjunctive to
thrombolytic therapy where brain function is still arguably salvageable.
Transcutaneous
cranial vibration to the vascular regions of the brain of the patient 20 are
readily
42
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA20041001621
achieved by the methods below. The underperfused body region in this case is
the organ
and tissues of the brain of the patient 20. The vibrator 10 (with preferably a
pair of
contacts 12) is advantageously attached to the posterior aspect of the neck of
the patient
20, however the lateral or posterolateral aspects of the neck may also be
used.
Alternatively, vibration may be applied directly to the craniunz of the
patient 20 via a
helmet (not shown), cushioned to avoid bruising to the head of patient 20,
which
comprises an altemative attaclunent interface to vibrator 10. A frequency of
less than
1000 Hz, and preferably selected from the 1- 120 Hz range, is then applied at
a selected
displacement amplitude (i.e. from 1 mm to 15 mm displacements), in conjunction
with a
systenucally delivered drug such as a thrombolytic, anti-platelet,
anticoagulant, or vaso-
dilatory drug. The choice of 50 Hz sinusoidal vibration is preferred, as 50 Hz
sinusoidal vibration can be delivered at a relatively high displacement
amplitude, and is
a well established frequency Imown to produce cavitation and acoustic
streaming (to
assist in thrombolytic to clot filtration), as well as vascular dilation and
clot disruption.
As an option, square wave <b>, saw tooth wave <c>, exponential wave <d>, or
any
linear or nonlinear displacement wave form (or combinations thereof) may be
used (see
Figure S). The displacement amplitude of vibration should be selected
judiciously with
the niore serious natured acute ischenuc strokes (i.e. where there is a
traumatic deficit
noted), preferably receiving relatively higher displacement anlplitudes in
keeping with
an increased benefit to risk ratio (i.e. benefit of improved thrombolysis to
restore vital
function vs. risk of cerebral bleeding). Optionally, vibration therapy may be
utilized
independently (i.e. without a drug), or with a decreased dosage of drugs.
Vibration therapy in accordance with the present invention may be further
utilized to facilitate the restoration of blood flow in acute, emergent
peripheral arterial
obstructions such as those occurring in the limbs of a patient. When the
obstruction
(which is usually thrombo-embolic in nature or involving acute thrombosis on a
preexisting ulcerative plaque) involves a critical segment of the arterial
system where
the collateral potential of blood perfusion is poor, the clinical picture is
dracnatic with
loss of limb viability and aniputation inuninent if not treated effectively
within six
hours. Transcutaneous peripheral vibration to the vascular region of the
effected
peripheral body part (including all organs and tissues distal to and including
the
clavicles and groin region of the patient 20) are readily achieved by the
methods
disclosed below. A vibration frequency of less than 1000 Hz, preferably 1-120
Hz, and
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CA 02540439 2006-01-27
WO 2005/023121 PcT/ca2004/001621
optimally 50 Hz sinusoidal vibration, is applied transcutaneously to the
presumed culprit
area, at a high force or displacement amplitude (preferably at the highest
levels deemed
tolerable and safe to the patient 20). As an option, square wave <b>, saw
tooth wave
<c>, exponential wave <d>, or any linear or nonlinear (or combination thereoi)
displacement wave form, may be used (see Figure 8). Vibration therapy is
preferably
used in conjunction with pharmacologically active a,ents such as
thrombolytics, anti-
platelets, vaso-dilatory or anticoagulant drugs as a first line method to
restore early flow,
and to also act as a bridge to emergency corrective surgery or intervention. A
singular
or plurality of contacts 12 are utilized to provide maximal agitative
vibration energy
imparted to the culprit area. The contacts 12 are placed on the limb surface
affected,
with contact preferably established at the point at which distal pulses are
lost. Tvpical
attachment areas comprise the pelvis/groin area (i.e. iliac and femoral
arteries), thigh
(femoral artery), popliteal space (popliteal artery), lower leg (tibial
artery), periosteum
of the clavicle and first rib (sub-clavian artery), soft tissue area between
the clavicle and
trapezius muscle (sub-clavian artery), axilla (axillary artery), brachium
(brachial artery),
anti-cubital fossa (brachial artery), and forearm (radial artery). The
contacts 12 are
advantageously comprised of silicone rubber, however any commercially
available
material, preferably resilient and substantially non-distortable may be used
to form the
contact surface of contacts 12. Altematively, the contact surface of specially
adapted
"peripheral" contact heads (not showil) are malleable to enable a more
exacting vibration
contact to complex, uneven and rigid contours (such as in contours overlying
or directly
adjacent to bone) of the body surface of the patient 20. The peripheral,
contact heads in
this variation (which are of a known type) are comprised of a solid base
piece, which
partially encapsulates an incompressible fluid with a semi-compliant membrane
overlying the active end of the base piece and incompressible fluid. For acute
peripheral
vascular obstruction applications, the engagement means of vibrator 10 may be
by hand,
by clamp 100, or alternatively via a belt engagement system with VelcroTM
strap
securement (described later). Ultrasonic imaging means to target a culprit
blood clot
within a culprit vascular region may be employed to enable direct
visualization and
targeting of the vibration therapy with highest efficiency. The application of
vibration
optionally commences with adjunctive drug therapy until signs of reperfusion
or until
invasive corrective measures may be established. Optionally, vibration therapy
mav be
utilized independently (i.e. without a drug), or with a decreased dosage of
drugs.
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Referring again to Figure 1, the preferred embodiment of the vibrator 10 (i.e.
in
the emergency treatment of ST elevation NII) is applied by the hands of an
operator with
the patient 20 lying substantially in the supine position.
The preferred vibrator 10 of the present invention is operable to generate and
emit vibration selectably in the 1- 120 Hz range. A second variant "research"
vibrator
(i.e.-"variant 2"- not shown), is also prov-ided, being adapted to operate in
a higher
frequency range, above 150 fL, and up to 1000 Hz (which is designed primarily
for
research applications and applications directed by ultrasonic imaging). Tlius,
vibration
therapy within the range of 1-1000 Hz is provided according to the invention.
Vibrator 10 contains a high powered linear stepper motor (not show-n - located
within housing 14), with sufficient power to enable operation at engagement
forces of up
to approximately 100 N. Vibrator 10 is characterized to enable selective
frequency and
displacement aniplitude control in the 1 - 120 Hz and 1- 15 mni range
respectively, as
well as selectable displacement "wave fotm" control (comprising a selection of
sinusoidal <a>, square <b>, saw tooth <c>, and exponential <d> wave shapes -
see
Figure 3.). Vibrator 10 is farther programmable to emit any other linear or
nonlinear
displacenient wave shape (or combination thereof). Use of vibrator 10 enables
the
delivery of high amplitude forces of vibration concentrated to the selected
body surface
treated.
The active end of the provided linear stepper motor is operatively linked with
and drives the proximal "non-active end" of shaft 16 (not shown - within
housing 14),
which is thereafter projected through housing 14 (now shown), to enable
contact with
the selected attachment interface. As an option, a displacement amplifier
(such as a
lever or a pneumatic displacement amplification system) may be incorporated to
establish the necessary displacement amplitude eniission required.
The selection of displacement amplitudes ranging from 0 (off), 1 to 15 mm
deflection is provided by an amplitude regulatory mechanism which is
incrementally
controlled by the operator. The amplitude regulatory mechanism is enabled by
the
provided linear stepper motor stroke length control. The stroke length control
is
coordinated via commands from processor 34 and interface 50, which all taken
together
comprise the "amplitude regulatory mechanism" of vibrator 10. Vibrator 10 is
also
optionally programmable to enable selectable vibration force (or power)
control at a
CA 02540439 2008-06-02
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given frequency, as an alternate to (or in addition to) the provided
selectable displacement
amplitude (or stroke length) control.
Operation of the preferred vibrator 10 is as follows. The operator inputs
commands
to the interface 50, which thereafter sends commands to processor 34, located
upon and
within (respectively) housing 14 of the vibrator 10. Commands from interface
50 to processor
34 indicate the operator selection of various vibration signal parameters such
as emission
frequency (i. e. 0 off, 1-120 Hz), vibratory displacement wavefonn emission
shape (i.e.
sinusoidal <a>, square <b>, saw tooth <c>, or exponential <d>-see Figure 8. ),
and stroke
length (i.e. 0 off, 1-15 mm deflection). Processor 34 (with signal generator
and amplifier)
generates the appropriate signal at the appropriate power level to feed the
input of the
provided linear stepper motor.
As an option, vibrator 10 will also contain programming and controls to enable
the
selection of variable frequency response algorithms (or variations in
vibration cadence), such
as in the Sharper Image Massager Model HF 757.
A fan (not shown) is advantageously disposed within housing 14 of vibrator 10,
(as
well as a pair of ventilation holes through housing 14-also not shown), to
assist convective air
cooling of the provided linear stepper motor therein, which enables prolonged
application
times such that the device will not overheat. Alternatively, any otlier known
suitable cooling
mechanism tnay be used. Vibrator 10 is also optionally equipped with a
controllable heating
system for heating the contact surface of contacts 12, which may add benefit
to clot disruption
in superficial treatments of thromboses. Any one of the amplifier or signal
generator within
processor 34 or interface 50 (in any combination) may optionally be disposed
remote from
housing 14 of vibrator 10, such as to enable a more compact and lighter weight
hand held
instrument.
Vibrator 10 is powered by an AC power cord, or as a second means via a
portable
DC battery pack (not shown), which is slide-ably and removably disposed within
the handle
of housing 14. The DC battery pack is advantageous as it enables operation of
vibrator 10 in
the field wherein no AC power is commonly available.
It should be emphasized that vibrator 10 as herein described comprises a
"preferred"
means (or apparatus) for the deliverance of emergency vibration therapy in the
treatment of
acute vascular obstructions, and accordingly may be varied in many ways to
enable function
of an effective emergency response system. In essence, any low
46
CA 02540439 2006-01-27
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frequency non-invasive vibrator (or percussion, or oscillation device by other
name)
with an attaclunent interface suitable to enable direct selected bodv surface
contact,
operational in the rangge of 1- 120 Hz (and optunally within the range of 20 -
120 Hz),
with a displacement amplitude enablement of greater than 2 nun (and preferably
geater
i than 4 mm), which is operable under engagement forces at least 5 - 10 N(and
preferably
geater than 20 N), may be used to provide an effective emeraency tool in the
emer.-ency response system. Possible variations to vibrator 10 for enablement
of tlie
eniereency system are described later.
The variant research vibrator ("variant 2") of the present invention contains
a
higli powered voice coil adapted to generate vibration at higher frequencies
within the 1
- 1000 Hz range. The variant research vibrator ("variant 2"), is characterized
to enable
both selective frequency and force (or power) control at a given frequency,
and is also
operational under engagement forces to the human body of up to about 100 N.
Frequency settings above 150 Hz have limited displacement amplitude enzission
capability, in keeping with clinical safety concerns and the mechanical
constraints of the
provided system, and are thereby confined to the low millimeter to sub
millimeter
emission ranges (i.e. as low as about 0.1 mm). The provided high powered voice
coil
(ivhich is located witlun a housing adapted in size and shape for hand held
use) is
operatively linked to the proximal "non-active end" of the vibratory shaft of
the variant
research vibrator ("variant 2"). The vibratory shaft is thereafter projected
through the
housing, enabling removable attachment to any of the attachment interfaces
described
according to the invention. The variant research vibrator is also powered in
like fashion
to the preferred vibrator 10 (as described above); through AC power cord and
removable
DC battery pack. The variant research vibrator is of preferred use in
conjunction with
simultaneous ultrasonic imaging (as per the dual function system - described
earlier), as
the low displacement amplitude signal at higher frequencies requires direction
and the
establishment of a sonic penetration window, to ensure therapeutic penetration
to target
vascular areas within the patient 20.
It should be understood that the choice of a voice coil is not critical to
enable
vibration therapy in the 1- 1000 Hz range, and a high powered peristaltic
linear motor
for example with frequency and power (or force / stroke) control, may
alternatively be
employed. An exemplary peristaltic linear motor may be comprised of a
magnetostrictive niaterial optimally incorporating Terfenol D. Alternatively,
a linear
47
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA200.1/001621
stepper motor assembly could be used independently, or in conjunction with the
magnetostrictive material.
A variant "light weight" vibrator (i.e. "variant 3" - not shown) is also
provided
according to the invention (described later), which enables maximum
displacement
amplitude emissions limited to 10 mm deflections with sufficient power to
enable
operation under engagenient forces to the body surface of the patient 20 of up
to about
50 N. Variant light weight vibrator 10 ("variant 3") is of like design to
vibrator 10, but
is of lighter weiaht (i.e. with a smaller, less powerful linear stepper motor)
and is
thereby better suited for self administration by the patient 20, who may be
too weak to
hold a heavier device.
Yet another variant "heavy duty" vibrator (i.e. "variant 4" - not shown) of
like
design to vibrator 10 but of greater weight and of higher power (i.e. with a
larger, more
powerful linear stepper motor) is provided for obese patients (or when the
backside of
the patient 20 is utilized) and will not dampen its oscillations when
engagement forces
of significantly greater than 100 N are applied.
The preferred vibrator 10 is of a size and weight well suited for clamp 100
engagement, belt engagement (described later) or engagement by the hand of an
operator
preferably via a double-Iianded tecluuque. The variant lightweight vibrator
("variant 3")
is of a size and weight well suited to single hand or double handed
engagement. The
variant heavy duty vibrator ("variant 4") is of a size and weight more suited
to clamp
100 engagement, or engagement by both hands of an operator. The variant heavy
duty
vibrator ("variant 4") is well suited for use with obese patients, or in cases
where the
backside of the patient 20 is utilized (described earlier), wherein higher
displacement
amplitudes and engagement forces may be required to ensure therapeutic
penetration.
The housing 14 of vibrator 10 (and all provided variants) is advantageously
made of ABS Cycolac (TM) material, however any alternative durable and
lightweight
material (such as polycarbonate or stainless steel) may be used.
The preferred vibrator 10 (and provided variants) is powered by battery or
power cord at a range of voltages (e.g. North America - 110, 120 V, Europe -
220V,
Japan 95, 105 V, Australia 240 V) and is (as stated) operable both by battery
and power
cord for emergency settings. The vibrator 10 (plus all provided variants),
cumulatively
enables a selection means for a range of frequencies in increnients of 0
(off), 1, 5, 10,
48
CA 02540439 2006-01-27
WO 2005/1123121 PCT/CA2004/001621
20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 150, 200, 300, 400, 500, 600,
700, 800, 900
and 1000 Hz (although other variations in frequency selection mav be
employed).
Detachable contacts 12 are provided in a plurality of sizes, (i.e. small,
medium
and large), and made substantiallv of silicone rubber, however any resilient
yet non-
obtrusive material (preferably shaped with a convex contact surface), to allow
conifortable application against the body of patient 20 may be used. The
contacts 12 are
sized to make contact with an intercostal space of the human body, and rest
evenlv
against the upper and lower rib, with an outward dome shaped conveYity to
ensure soft
tissue contact and concentrate vibration therapy effectively. The preferred
contact 12
advantageously comprises a semi spherical dome shape, with a flat planar
circular base
(the base being of similar size to the head of a stethoscope), wherein the
base ranges in
size between 2 cm, 3 cm and 4 cm diameter. It should be understood that the
exact shape
of contacts 12 (i.e. a semi spherical dome) is not critical, and that any
convexly shaped
contact head may be used, as long as efficient seating within the intercostal
spaces of the
patient 20 is enabled. Optionally, a variety of contacts comprising suction
cups (not
shown) are provided to enable an additional active retraction force, provided
the patient
is not significantly diaphoretic. A soft rubber lining (or more specifically,
a vinyl
lining with foam rubber underlay of l:nown type) may optionally overly the
enga-ement
surface of contacts 12 in order to impart a more comfortable application
(which is
20 especially useful for extremely tender skinned females with fleshy breast
tissue who
often are very sensitive to pressure applications to the chest wall). It
should also be
understood that the exact size of contacts 12 is not critical, and a selection
of variant
contacts (not shown) with even smaller contact surfaces may be used, enabling
a direct
seating within the rib space of the patient 20 such that the ribs themselves
are minimally
or not touched. This manner of chest wall contact provides a more comfortable
application for some individuals.
The preferred embodiment comprises a pair of adjustably spaced contacts 12,
separated by bifurcated connector 13 which is attached to shaft 16 of vibrator
10, to
provide concentrated therapy (preferably) to either side of sternum at tlle
selected
intercostal space as per the prescribed methodology. Alternatively, to avoid
unnecessary
brnising (or trauma) to the chest wall, a solitary contact 12 (either attached
directly to
shaft 16 or via the variant connector - described earlier) placed leftward the
sternum can
be utilized, this method particularly suitable in cases of known Anterior or
Lateral ANII
49
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA200-1/001621
(i.e. wherein leftward coronary involvement is diagnosed). In a further
variation, to
optimize sonic penetrability to the heart and to account for variable location
of the heart
within the tlloracic cavity, a plurality beyond a pair of contacts 12 may be
used. In this
case, bifurcated connector 13 further utilizes the incorporated support
structure 24
(depicted in Fiwre 4), to allow for the addition of up to two slide-able and
lockable
sleeves 23, wherein each sleeve 23 incorporates a pair of support arms 22,
with each
support arm disposing at least a single contact 12. Placement of the plurality
bevond a
pair of contacts 12 could be, for example along, or just lateral to the
anatonric right and
left sternal border, encompassing the 3rd, 4th and 5th intercostal spaces. In
yet another
variation, variant connector 19 disposing two pairs of adjustably spaced
contacts 12,
may be applied to bridge the sternum along the 3rd and 4th intercostal spaces,
along the
4th and 5th intercostal spaces, or even along the 3rd and 5th intercostal
spaces of the
patient 20.
To maximize sonic penetrability in particular to the left anterior descending
artery, the vibrator 10 and chosen attachment interface may be placed more
anatomically
leftward with respect to the patient 20, such that one or more contacts 12
will interface
with the left mid clavicular line (or thereabouts). Alternatively, any one of
the utilized
contacts 12 mav be slide-ably placed more Iateraliy along any one of the
chosen
anatomically leftward oriented support arms 22 (i.e. relative to patient 20),
with the
position of vibrator 10 remaining substantially over the stemum of patient 20.
In yet a
further variation, stimulation of the left mid clavicular line of the patient
20 may be
ensured via the use of a second vibration device with second attachment
interface,
preferably running in phase with the vibrator 10 (or equivalent) to avoid
destructive
interference of the vibratory signal
Referring again to Figure 7, peripheral devices to variant cardiac phase
controlled vibrator 11 ("variant 1") are required for use of the "advanced
method"
variation of the invention. The advanced method is specifically designed for
cardiac
use, to enable cardiac phase controlled vibration therapy (timed in accordance
to the
cardiac cycle) and the optional use of frequency algorithms to optimize the
system.
Display monitor 52 (located remote to the housing of variant cardiac phase
controlled vibrator 11 <"variant 1">) receives output from variant interface
51, and
peripheral physiologic sensors (as specified below) via variant processor 35.
Display
monitor 52 displays: ECG 36 output (up to three leads, e.g. V lead (anterior),
Lead lI
CA 02540439 2006-01-27
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(inferior) and V5 (lateral)); a digital readout of heart rate; external
accelerometer 39
wave form output comprising the delivered surface vibration displacement
amplitude on
the `vertical' axis in (mm), and a real time display moving right to left at
25 mrn/second
to match the waveform output of ECG 36 in real time on the `horizontal' axis;
the
waveform output of optional impedance plethysmograph 40 also moving in real
time to
match the output of ECG 36 (to monitor relative real time blood pressure, and
inspect
for timing of diastolic therapy); optional phonocardiography system 42 signal
trace; the
chosen frequency and niode of delivery (written annotations); the chosen
displacement
amplitude of the therapy (ivritten annotation); and optionally a noninvasive
blood
pressure wave form output also moving in real time to match ECG 36 wave form
output
via noninvasive blood pressure apparatus 44 arterial tonometry, to support an
absolute
value to the otherwise relative plethysmography wave form analogue. As an
alternative
to arterial tonometry, a noninvasive automatic blood pressure cuff system may
be used,
wherein a periodic digital readout of systemic blood pressure may be displayed
on
display monitor 52.
Variant interface 51 comprises a combination of an electronic control touch
screen and keyboard entry which is (as stated previously) also located remote
to variant
cardiac phase controlled vibrator 11 ("variant 1"), and is preferably placed
alongside
display monitor 52 and variant processor 35 on a portable work bench or stand
(not
shown). Variant interface 51 enables the reception of input from the operator
and
supplies the interface with variant processor 35. Variant interface 51 is
adapted to
receive and transmit infomiation relating to: the mode of vibration to be
delivered (i.e.
continuous, or diastolic only vibration); the displacement amplitude of
vibration (0 off, 1
-15 mm displacements); the displacement amplitude of vibration according to
cardiac
phase (0 off, 1-15 mm displacements); the frequency of vibration (0 off, 1-
120 Hz);
the frequency according to cardiac phase; the displacement wave form type
(i.e.
sinusoidal, square, saw tooth or exponential); the fine tuning control of
vibration
emission timing (or "vibration emission timing control"); the preferred ECG 36
lead to
be utilized for deternunine or "tracking" the QRS complex via variant
processor 35; and
an electrocardiographic low pass frequency filter (i.e. with 40 Hz cutoff)
suitable for
eliminating muscle tremor and vibrational artifact from the resultant ECG 36
trace prior
to processing via variant processor 35.
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Variant processor 35 receives information from the physiological monitoring
and sensing equipment and variant interface 51, and provides output to display
monitor
52 and variant cardiac phase controlled vibrator 11 ("variant 1"). A
preproerammed,
default rate related time delay tracking the deflection of the QRS complex
(used to
signify and electronicallv trigger the onset of diastolic vibration) is
provided bv variant
processor 35 progrannnable control. Variant processor 35 thereby is enabled to
determine systolic and diastolic phases based on ECG 36 output. The beginning
of the
diastolic phase of vibration is further adjustable by the operator according
to an
additional operator input (or vibration emission timing control) to variant
interface 51.
based on information gained by phvsiological timin' parameters as viewed on
display
monitor 52. These timing parameters are represented by; the wave form produced
by
accelerometer 39 on shaft 17 (which defines the timing and amplitude of the
applied
vibration), the wave fomz produced by ECG 36 (which defines the beginning of
systole
via the onset of the QRS complex), and optionally impedance plethysmograph 40
(which
defines the beginning of diastole via the dichrotic notch of the arterial wave
form
analogue). As a furtlier option, phonocardiogram 42 is used to define witll
more
exacting precision the onset of diastole (i.e. via the initial split of the
"S2" heart sound
signifying closure of the Aortic Valve). Phonocardiogram 42 however is not
usefut in
continuous mode vibration therapy because of the continuous vibration noise,
which
= 20 contaminates the signal. In the case where both impedance plethysmograph
40 and
plionocardiography system 42 are not employed, the onset of diastole can be
approximated as (and/or verified by) the temiination of the T wave as seen on
the
waveform output of ECG 36. Variant processor 35, upon receiving input from
variant
interface 51, and upon receiving information from the physiological monitoring
and
sensing equipment, will process the information and provide output to variant
cardiac
phase controlled vibrator I 1("variant 1") which applies the selected timing,
mode,
displacement wave form, frequency and displaeement amplitude of vibration
therapy.
ECG 36 comprises a six electrode system, with a left arm, left leg, right arm,
right leg (ground) and an anterior pre-cordial lead (modified V lead
preferably placed on
the stemum) and a lateral pre- cordial lead (V5). Output from leads II,
modified V lead,
and V5 are preferably displayed on display monitor 52. Any lead may be
selected for
variant processor 35 autanlatic tracking of the QRS complex, with the lead
presenting
with the tallest QRS complexes and / or relatively smallest T waves preferred
to ensure
52
CA 02540439 2006-01-27
WO 20115/023121 PCT/CA2004/00 1621
appropriate tracking and avoid "double counting". In an option, a pair of ECG
electrodes may be advantageously incorporated within or mouated upon the
contact
surfaces of the contacts 12, to enable an expedited nieans of obtaining
electrocardiographic infomtation.
Impedance plethysmograph 40 requires the placement of two electrodes on the
ami.s of the patient 20 and the application of a minimal current in order to
inonitor
relative changes of blood pressure in real time, checking, for example, for
any beneficial
inotropic effects with diastolic only vibration in cardiogenic shock patients,
or sudden
deterioration of blood pressure during treatment in an otherwise
hemodynamically stable
case of evolving myocardial infarction. The present invention eniploys a Tek-
troni.lTM
type 3C66 impedance plethysmograph system; however any known impedance
plethysmography system may be used for plethysmograph 40. Impedance
plethysmograph 40 is also employed to check the timing of the closure of the
aortic
valve and therefore the beginning of diastole, and is useful to confirm or to
facilitate the
manual adjustment (or vibration emission timing control) of the default rate
related time
delay set after sensing of the QRS complex to ensure that diastole is captured
properly in
the timing algoritluns. Alternatively, a variant photo plethysmograph (such as
the
TektronixT" Plethysmography Pulse Sensor) placed to the finger or forehead of
the
patient 20, with wave form signal output to display monitor 52 (to inspect for
inotropic
changes) may be employed. Impedance plethysmograph 40 is preferable as it
yields a
closer analogue trace of a central arterial wave form (i.e. yielding an closer
approximation of the true timing of Aortic Valve closure via the dichrotic
notch) than
the variant photo plethysmograph which incorporates an analogue trace of a
peripheral
arterial wave fom1.
Phonocardiograrn 42 is of a commercially known type, consisting of a small
nucrophone placed on the chest wall wluch provides output to display monitor
52
representing the heart sounds in time with ECG 36, plethysmograph 40 and
accelerometer 39 signals. The heart sound "S 1" represents the onset of
systole, and the
initial component (or "split") of the heart sound "S2" represents the onset of
diastole.
Phonocardiogram 42 can with extreme precision, provide the timing of aortic
valve
closure marking the onset of diastole, however the device is limited to
diastolic only
mode vibration therapy as continuous mode vibration contaminates the audio
trace.
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CA 02540439 2006-01-27
WO 2005/023121 PCT/CA21)01/001621
Noninvasive blood pressure apparatus 4=1 comprises a modern state of the art
arterial tonometry noninvasive blood pressure monitoring system (i.e. Pilot
arterial
tonometry device manufactured by Colin ivledical Instruments Corp.).
Optionally, a
noninvasive blood pressure monitor, comprising a blood pressure cuff system
which
takes a periodic blood pressure reading fronr the arm of the patient 20 and
displays the
information on display monitor 52. may be used. Vibration therapy, in this
latter
example, n13.y be programmed to temporarily cease during the measurements of
the
blood pressure cuff system to avoid interference in the audio blood pressure
nieasurements.
External accelerometer 39 (i.e. Shin Nipon Sokki C. Ltd Enuc 540) is placed on
shaft 17 of variant cardiac phase controlled vibrator 11 ("variant 1") to
monitor the
timing, frequency and displacement amplitude of emitted vtbration from variant
cardiac
phase controlled vibrator 11 ("variant 1"). Optionally, transesophageal
accelerometer
38 (i.e. Shin Nipon Sol:ld Co. Ltd Emic 540M) placed on a transesophageal lead
is used
to monitor chest wall penetration of low frequency vibration to behind the
heart.
Alternatively, any commercially available niiniature accelerometers can be
used for
either application.
A strain gauge force transducer (not shoNvn) or optionally a weight scale to
indicate the engagement force of contact or contacts 12 against the chest wall
(or other
body part) of the patient 20 is optionally provided.
It should be understood that the location of variant interface 51, display
monitor
52 and variant processor 35 relative to variant cardiac phase controlled
vibrator 11
("variant 1") is not critical to enable use of the advanced method, and is
provided as
separate distinctly located elements (e. e. on a portable workbench) only to
facilitate
operative links between the instruments and necessary sensing and nionitoring
equipment which may be quite extensive (especially in the case wherein all
possible
sensing and monitoring equipment are utilized). For example, in an alternative
embodiment, variant cardiac phase controlled vibrator 11 may be altered to
comprise a
functionally self contained operator held unit (or device), comprising a
display means
(such as a LED display on the housing of the device), a control means (such as
control
switches on the handle of the device), a cardiac phase monitoring means (such
as an
ECG monitor operable in conjunction with or as part of the device), a
vibratory emission
monitoring means (such as an accelerometer system placed on a vibratory
component of
54
CA 02540439 2006-01-27
WO 20115/1123121 PCT/CA?004/001621
the device or altematively a vibration emission indicator), and a processing
means (such
as a microchip or other prog,rammable logic controller located within the
housinQ of the
device)_ This "self contained" arrangement of the cardiac phase controlled
vibration
delivery system may be advantageous to an operator (or paramedic) in the
field, wherein
maneuverability and ease of portability of the utilized apparatus are
important factors
towards expediency and effectiveness in emergency situations.
Referring now to Figure 9, a perspective view of a variation of the preferred
embodiment, a hand held single imaging ! treatment probe (herein set forth as
the
"variant dual function imaging vibration device 15"), and method as applied to
the
patient 20 is shown. Tlus system (as per the "dual function system" described
earlier)
employs both low frequency vibration and high frequency ultrasonographic
imaging
(HFUS) taken together in concert (simultaneously) via a single combined hand
held
transmission unit, for visually directing low frequency vibration therapy
within the body
of the patient 20. The attachment interface of variant dual function iniaging
vibration
device 15 contains an ultrasonic imaging transducer (not shown - located at
the active
end of variant dual function imaging vibration device 15, proximate patient
20),
whereby an image can be viewed on ultrasonographic 2-D display 17. The
ultrasonic
imaging transducer is operatively connected (or acoustically coupled) to a low
freauency
vibration source (also not shown - located within the housing of dual function
imaging
vibration device 15) such that upon activation, when the low frequency
vibration source
generates vibration, the ultrasonic imaging transducer vibrates and thereby is
enabled to
deliver low frequency vibration simultaneously (i.e. together in real time)
with HFUS
imaging, all via a shared contact surface to the patient 20. An optional
weight added
within or exterior to the housing of variant dual function iniaging vibration
device 15
(weight not shown), adds inertia to the system to ergonomically assist the
operator (i.e.
to apply engagement force) during hand held placement of dual function imaging
vibration device 15. An example of a useful ultrasonic image 1S (in this case
an image
of the heart is depicted), is shown on ultrasonographic 2-D display 17.
The vibration source of the-variant dual function imaging vibration device 15
advantageously comprises the same active components of preferred vibrator 10
(described earlier), and thereby enables selectable displacement amplitude and
selectable displacement wave form control within a 1-120 Hz range. It should
be
understood however that this particular selection of vibration source is not
critical to
CA 02540439 2006-01-27
WO 211115/023121 PCT/CA2004/001621
enable use of the dual function system, and any Imown vibration source
operable to
oenerate vibration within the 1- 1000 Hz range (so long as the therapeutic
vibration
wave form does not disable or interfere with the necessary ultrasonic imaging
wave
form) may be used, regardless of the level of provided vibratory emission
control. Such
vibration sources may for example comprise but not be limited to; linear
stepper motors,
linear stepper motors with displacement amplification, linear (non- stepper)
motors,
rotary nlotors with a rotary to linear conversion element such as a cam or
crank,
eccentrically spinning weights, magnetostrictive actuators, voice coils,
shakers (e.g. with
or without neodymium magnet transducers), and ceramic servo motors coupled to
either
a rotary (with cam) or linear stage. The preferred vibration source should be
operable at
high force or displacement amplitude settings while under load, such as to
optimally
enable a high energy penetrative system of vibration therapy (or oscillatory
or
percussive therapy by other name).
In a variation to the above dual function system (i.e. apparatus), a siniply
1i adapted ultrasonographic imaging transducer is provided, which is readily
incorporated
for use as an attachment interface via removable attachment to shaft 16 of
vibrator 10.
In reference to Figure 10, this variation of the dual function system utilizes
variant
"ultrasonographic imaging" contact. 60, advantageously comprisine semi
spherical
silicone dome 61 attached to and partially encapsulating a distal active end
of a pediatric
HFUS imaging transducer of known type. Rectangular slit 62 is centered at the
curved
"distal", contact surface of semi spherical silicone dome 61 to provide for a
minimal
protrusion of engagement face 63 (or imaging contact surface by other name) of
the
pediatric HFUS imaging transdueer. This arrangement enables stable contact of
both
engagement face 63 (i.e. for imaging), and the distal contact surface of semi
spherical
silicone donie 61 (i.e. for improved seating and transmission of low frequency
vibration)
to the chest wall, or other body part, of the patient 20. The "proximal" end
(i.e. away
from patient 20) of variant ultrasonograpliic imaging contact 60 coniprises
housing 64
for the electronic components of the provided pediatric HFUS imaging
transducer.
Hollow connecting column 6-i is attached to and projected from housing 64,
which
enables removable attachment (by friction) to shaft 16 of vibrator 10 (or to
the shaft of
any of the provided variations to vibrator 10 according to the invention);
however any
lmown means of attachment (fixed or removable) may be used, as long as a sound
vibratory connection is established. In this variation to the dual function
system, shaft
56'
CA 02540439 2006-01-27
WO 200-5/023121 PCTlCA2004/001621
16 once activated, vibrates connecting column 65, which vtbrates housing 64
for the
electronic components of the pediatric HFUS imagging transducer, which in tum
vibrates
attached semi spherical silicone dome 61 and enga~ement face 63, which taken
together
comprises variant ultrasonographic imagine contact 60. The electronic control
cord (not
shown) of the pediatric HFUS imaging transducer is optionally removably
secured to the
exterior surface of housing 14 of vibrator 10. The electronic control cord is
thereafter
removably attached to an ultrasound imaging apparatus (not shown) of known
type;
however any commercially available ultrasonic imaging apparatus may be adapted
for
use.
It should be understood that while ultrasonographic imaging contact 60 of the
dual function system incorporates the use of a partially encapsulating
structure (i.e.
semispherical silicone dome 61) disposed about the provided distal active end
of the
pediatric HFUS imaging transducer to improve contact and transmission of the
low
frequency therapeutic vibration, this arrangenient is not critical, and the
pediatric HFUS
imaging transducer (or any other known ultrasonic imaging transducer) may be
optionally applied alone (or by any other means), directly to the skin surface
of the
patient 20, without such an acconipaniment. Furthemzore, while a pediatric
variety of
HFUS imagintr transducer is preferred because of its smaller size (i.e. to
enable optimal
rib space application), alternatively, any known ultrasonic imaging transducer
adapted in
size and shape to enable human contact (preferably of a size to enable seating
within a
rib space) may be adapted for use.
As a further option of enablement to the dual function system (and yet another
variation), an ultrasonic imaging probe (or preferably variant
ultrasonographic imaging
contact 60 as described above) may be adapted for attachment to the
anatomically
leftward oriented (relative to patient 20) attachment site ofbifiucated
connector 13 of
vibrator 10 (or alternatively any equivalent bifurcated attachment interface
stenuning
from any low frequency vibration source operable to generate vibration in the
1- 1000
Hz range). This arrangement enables ultrasonic imaging guided placement via
the
preferred pair of attachment sites (i.e. to the chest wall of the patient 20),
wherein the
ultrasonic imaging transducer (or variant ultrasonographic imaging contact 60)
is placed
to an application site on the patient 20 comprising a determined feasible
sonic
penetration window (as per the methods described earlier), which will usually
be near
the sternal margin, at the anatomically leftward third, fourth or fifth
intercostal space.
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CA 02540439 2006-01-27
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The opposing (or anatoniically rightward oriented contact, which may or may
not
comprise an ultrasonic imaging transducer), is preferably placed anatomically
rightward
to the stemum at the same determined intercostal level, or optionally one
intercostal
spacer lower (or inferior) as per the methodology described earlier. It should
be
understood that the incorporation of one, or more than one ultrasonic imaging
transducer
may be used, in anv number of orientations according to the invention (i.e.
depending on
the style of attachment interface selected).
A"multifunetion systenf' is also provided, which in addition to providing a
means of transmission for low frequency vibration therapy concurrently and
simultaneously with ultrasonic imaging via a single transmission instrument
(i.e. as
above in the "dual function" system), further enables a LFUS treatment wave
form
emission. A variant "ultrasonographic imaging and LFUS treatment" contact (not
shown) adapted for removable attachment to shaft 16 of vibrator 10 (and
provided
variants), with low frequency ultrasonic treatment emission capabilities as
well as high
frequency ultrasonic imaging capabilities, is provided. The variant
ultrasonographic
imaging and LFUS treatment contact comprises an ultrasonic phased array
imaging
transducer mounted upon and acoustically coupled to the active surface of a
low
froquency ultrasonic transducer (both of l:now-n types), such as to enable
transmission of
the LFUS treatment wave form emission through the active components of the
ultrasonic
phased array imaging transducer, and thereby to the patient 20. The loxv
frequency
ultrasonic transducer (or "LFUS transducer") component of the multifunction
system
advantageously comprises a piezoelectric actuator which is operational to emit
a
frequency at 27 kHz, which is a frequency known for its superior tissue
penetration
characteristics and thrombo-disruptive properties (although other LFUS
frequencies
within the range of 20 - 1001cHz may be used, via the incorporation of
alternate
piezoelectric actuators). The LFUS transducer and ultrasonic phased array
imaging
transducer assenlbly work together simultaneously and nondestructively, to
supply
continuous high resolution imaging with HFL'S and simultaneous treatment with
a
LFUS wave form, all in conjunction with low frequency (i.e. sonic to
infrasonic range)
vibration therapy.
Variant ultrasonographic imaging and LFUS treatment contact, (as with variant
ultrasonographic imaging contact 60 - described earlier), is also removably
attached to
shaft 16 of vibrator 10 (or provided variant) by friction via a hollow
connector (not
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CA 02540439 2006-01-27
WO 2005/023121 PCT/CA2004/001621
shown), wherein in this case, the hollow connector is attached to the
"proximal" non-
active end of the LFUS transducer electronic housing. Alternatively, anv lmown
attachment means (removable or fi.Yed) mav be used, as long as a stable
vibratory
connection is established. A first electronic control cord joins the variant
ultrasonog=raphic imaging and LFUS treatment contact to an ultrasonic imaging
device,
and a second electronic control cord joins the variant ultrasonographic
imaging and
LFUS treatment contact to a LFUS control apparatus to enable an operator
control of the
function of the LFUS transducer of the multifunction system. A selectable duty
factor
between 1% and 100%, plus a selectable intensity level of between 0.5 W/ sq.
cm and 25
W/ sq. cm is provided to the operator via the LFUS control apparatus. The
preferred
LFUS treatment waveform comprises a frequency of 27 kHz, with a 100% duty
factor
emission at makimum tolerable intensity by the patient 20 in emergency
situations. A
temperature probe (not shown) is optionally attached to the periphery of the
engaQement
face of the variant ultrasonographic iniaging and LFUS treatment contact
(which equates
to the active contact surface of the provided ultrasonic phased array imaging
transducer)
in order to supply a readout such that the operator can adjust the duty factor
and / or
intensity levels of the LFUS treatment when (or if) the temperature at the
tissue interface
rises to an unacceptable level to avoid burning of the skin of the patient 20.
Alternatively, the variant ultrasonographic imaging and LFUS treatment contact
may be
eschanged, with the application skin surface cooled down by a wash cloth or
ice bag in
between variant ultrasonographic imaging and LFUS treatment contact exchanges.
In
tllis multifunction system embodiment, noninvasive low frequency vibration
(i.e. in the
sonic to infrasonic range), low frequency treatment ultrasound, and high
frequency
ultrasonic imaging are utilized nondestructively in concert (i.e.
simultaneously) to
provide an optimized therapy system for acute vascular obstructions and
treatment of
ischemic events, optimally employed as an adjunct to systemically delivered
drug
tlierapy, to improve localized drug effectiveness.
It should be understood that while the low frequency vibration source to the
multifunction system advantageously comprises the active components of
preferred
vibrator 10 (i.e. to enable a high degree of low frequency vibration control),
this
selection of low frequency vibration source is not critical to enable use of
the multi
function system according to the invention, and any known vibration source
operable to
generate vibration within the 1-1000 Hz range (so long as the therapeutic
vibration wave
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form does not disable or interfere with the necessary ultrasonic imaging wave
fornl, or
therapeutic low frequency ultrasonic wave forin) may be used, regardless of
the level of
provided vibratory emission control. Sucli vibration sources niay for example
comprise, but
not be limited to: linear stepper niotors, linear stepper motors with
displacement
amplification, linear (non stepper) motors, ceramic servo motors coupled to
either a rotary
(with cam) or linear stage, rotary motors with rotary to linear conversion
elements,
eccentrically spinning weights, magnetostrictive linear motors, voice coils,
and shakers (e. g.
with or without neodymium magnet transducers).
Furthermore, it should be understood that the type of LFUS transducer of the
multifunction system may be varied and a magnetostrictive actuator operable
within the 20-
100 kHz range may be used in the stead of the provided piezoelectric actuator.
Also, while the
embodiment shown (i. e. apparatus) provides a "variant ultrasonographic
imaging and LFUS
treatment contact "with an end to end acoustic coupling between the provided
LFUS
transducer and provided ultrasonic phased array imaging transducer (i.e. such
that the emitted
LFUS wave form is transmitted through the active components of the ultrasonic
phased array
iniaging transducer), alternatively other structural variations are possible
to enable use of the
multifunction system. For example, an ultrasonic imaging transducer may be
disposed around
or alternatively placed side by side to an incorporated LFUS transducer, such
that the active
ends (or engagement faces) of both units are directly adjacent to one another
and thereby
sharing a conimon application surface for contact to the patient 20. Treatment
applicators of
similar design to this are discussed in US patent 5,558, 092 to Unger et al..
The relative
geometry (i.e. ultrasonic imaging transducer disposed about the LFUS
transducer (or vice
versa) and the relative contact surface areas of the two complimentary
engagement faces are
not critical, as long as both the active contact surface of the LFUS
transducer and the active
contact surface of the ultrasonic imaging transducer are represented to a
sufficient degree to
enable their respective functions, and are placed in close proximity to one
another. Preferably
the shared contact surface provided would be of a size, and shape, to enable
efficient seating
in a rib space of the patient 20, to optimize use in transthoracic
applications.
As the cost of incorporation of an ultrasonic phased array imaging transducer
to
enable ultrasonic imaging for low frequency vibration directed therapy may be
prohibitive in
some medical centers, a more cost effective LFUS therapy concurrently
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA2004/001621
with the transmission of low frequency vibration therapy (i.e. a "dual
therapy"), without
ultrasonographic imaging capabilities is provided. This "dual therapy" option
to the
present invention comprises a variant "LFUS treatment" contact (not shown),
adapted
for removable attachment to shaft 16 of vibrator 10 (or provided variants
thereof),
wherein a semi spherical silicone dome advantaoeously attaches and partiallv
encapsulates a distal, active end of a low frequency ultrasound transducer
which is
operational at 27 kHz (although any low frequency ultrasonic transducer
operational
within the 20 - 100 kHz range, which is adaptable in size and shape to enable
seating
within a rib space may be used. A rectangular slit is centered at the semi
spherical
silicone dome's curved contact surface to provide for a nunimal protrusion of
the distal,
active surface of the low frequency ultrasound transducer's distal, active end
which is
advantageously slide-ably engaged there through. This arrangement enables
stable
contact of both the distal, active surface of the low frequency ultrasound
transducer and
the curved contact surface of the silicone dome, such as to enable optimal
transmission
of low frequency vibration and the LFUS therapeutic signal to the chest wall
(i.e. within
the rib spaces) and / or other body part treated. Optionally, the distal,
active surface of
the low frequency ultrasound transducer is adapted in size and shape, such as
to seat
uniforn-dv within a selected rib space of the patient 20, and tlius
eliminatinu the need of
an accompanying silicone dome, which serves only to optimize seating and
transmission
of the low frequency vibration aspect of the dual therapy. The non-active
"proximal"
end of the variant LFUS treatment contact the housing for the electronic
components of
the provided low frequency ultrasound transducer, wherein a hollow connecting
column
is attached which enables removable attachment of variant LFUS treatnient
contact to
shaft 16 of vibrator 10 (or provided variants thereof). In this LFUS dual
therapy option,
shaft 16, once activated, vibrates the connecting colunm which thereafter
vibrates the
housing for the electronic components of the low frequency ultrasound
transducer,
which in turn vibrates the attached distal, active surface of the low
frequency ultrasound
transducer and the attached silicone dome, which taken together, comprises the
variant
LFUS treatment contact. The simultaneous delivery of a low frequency
ultrasonic wave
form and low frequency vibration therapy (i.e. in the sonic to infrasonic
ranges) via a
conunon application surface is thus enabled.
Altematively, in a variant assembly, a pair of LFUS treatment contacts are
slide-ably and lock-ably niounted along the length of a variant bifurcated
connector (not
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CA 02540439 2006-01-27
WO 2005/1123121 PCT/CA2004/001621
shown), such as to enable bridging of the sternum of the patient 20, as per
the preferred
niethod of attachment in cardiac applications. In still another variant
assembly. a
plurality beyond a pair of LFUS treatment contacts may be eniployed to enable
placement to a plurality of intercostal spaces.
Lilce in the aforementioned "multifunction system" a selectable duty factor of
between 1% and 100%, and selectable intensity level of between 0.5 WI sq. cm
and 25
W/ sq. cm, is provided to the operator via a LFUS control apparatus in the
LFUS dual
therapy system. A temperature probe placed at the periphery of the active
contact
surface of the low frequency ultrasound transducer (i.e. wherein the active
contact
surface interfaces with the skin of the patient 20) is optionally provided
with a readout,
such that the operator can adjust the duty factor and intensity levels when
(or if) the
temperature at the tissue interface rises to an unacceptable level to avoid
burning of the
skin of the patient 20. Alternatively, the variant LFUS treatment contact may
be
exchanged, with the application skin surface cooled down by a cool wash cloth
or ice in-
between variant LFUS treatment contact exchanges.
The provided low frequency ultrasound transducer in the dual therapy variation
employs a piezoelectric actuator, however alternatively a magnetostrictive
elenient
(preferablv operational within the ranae of 20 - 100 kH-7), may be used to
enable the
method and dual therapy system. It should also be understood that wlule the
embodiment shown (i.e. apparatus - the LFUS treatment contact) preferably
incorporates
the use of a partially encapsulating structure with a slit disposed about the
provided low
frequency ultrasound transducer, this arrangement is not critical and the low
frequency
ultrasound transducer may be optionally applied alone (or by any other means),
directly
to the skin surface of the patient 20, without such an accompaniment. In this
"dual
therapy" option, low frequency vibration (i.e. in the sonic to infrasonic
range) and low
frequency ultrasound (without high frequency ultrasonic imaging) are utilized
nondestructively in concert to provide an optimized therapy system for acute
vascular
obstructions and ischemic events, optimally employed as an adjunct to
systemically
delivered drug tlierapy to iniprove localized drug effectiveness.
In the preferred enibodiment, (which utilizes low frequency vibration solely
in
the sonic to infrasonic ranges), vibrator 10 is secured to patient 20 by the
hand or hands
of an operator, wherein an alternative means of engagement employs use of
clamp 100.
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Referring now to Figure 11, a perspective view of a variation of clanip 100,
namely "clamp 101" is shown. Clamp 101 is used to attach vibrator 10 to the
chest wall
for cardiac applications or for any body part. The clamp 101 is made of steel,
but mav
alternatively be made of aluniinum or any other suitable material which can
supply
sufficient strength and stiffness to maintain the necessary position of
vibrator 10 and
application force to patient 20. Clamp 101 optionally comes with board 104,
which can
slide underneath a supine patient's back. Base 102 is preferably placed on top
of board
104. A vertical hollow bar 103 extends at substantially 90 degrees from base
102. An
extendable arm 105 extends horizontally from hollow bar 103, and can be slide-
ably
moved up and dowm hollow bar 103 to accommodate different sizes for patient
20. Once
positioned extendable arm 105 is locked in place to hollow bar 103 with
locking k-nob
107, however other mechanisms such as a clip or notch niay be used. Extendable
arm
105 in this variation is non-rotatable about the longitudinal axis of hollow
bar 103 and
advantageously comprises an angle bracket to provide a more stable platform
for
vibration therapy. Weight 114 is optionally placed on extendable arm 105 to
add further
inertia to clamp 101 if required. Sleeve 116, which articulates with and
supports
vibrator 10, is slide-able along extendable arm 105. Sleeve 116 includes
locking knob
109, wliich tiahtens to lock vibrator 10 in place alone extendable arm 105.
Vibrator 10
is selectively lowered and raised with engagement screw 110, which articulates
with and
vertically transverses sleeve 116 via a vertical screw column (not shown).
Engagement
screw 110 comprises an upper end disposing a turning knob, and a lower end
that
attaches the proximal, non-active end of housing 14 of vibrator 10. Set screw
119 is
provided to abut against engagement screw 110 thereby locking it in place
during
operation. Rotatable circular piece 118 in articulation with the lower end of
engagement
screw 110 and disposed at the surface witliin the non-active end of housing 14
is
provided such that liousing 14 may remain stationary while engagement screw
110
screws vibrator 10 up or dmvn. The exact dimensions of the components of clamp
101
(or 100) are not critical, as the height of the vertical support of vibrator
10 and the
horizontal distance of vibrator 10 along extendable arm105 (and arm 10S) is
made
adjustable.
The force of engagement of vibrator 10 is optionally evaluated by a strain
gauge
force meter (not shown) or in a variation a weight scale (not shown).
Optionally, a
pivoting, rotating and locking universal joint (not shown), located at the
juncture
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CA 02540439 2006-01-27
WO 2005/023121 PCT/CA20114/001621
between the non-active end of the housing 14 and the lower end of engagement
screw
110, allows for the adjustrrtent of the correct angulation and orientation of
vibrator 10
relative to engagement screw 110, to ensure a perpendicular contact between
the
attachment point of the contacts 12 and the chest wall (or other body part
treated),
wherein the patient 20 may not always rest perfectly supine or lying flat.
Universal joint
adjustments comprising angulations of less than or equal to 20 degees (i.e.
from the axis
of the engagement screw 110) are recommended to ensure structural stability of
clamp
100 or 101 engagement of vibrator 10 to the selected treatment body surface of
the
patient 20.
In both the clamp 100 and 101 variation of engagement, an emergency quick
release system comprising a mechanical lever (not shown) disposed to the
underside of
sleeve 116 is provided sucli that the screw column wluch is intetnalized
within the
vibrator sleeve 116, can be quickly disengaged by the mechanical lever from
engagement screw 110, thus (once quickly releasing set screw 119) liberating
vibrator
10 from the patient 20. Alternatively, a quick unlocking and detachment means
(not
shown) of vertical bar 106 (and / or hollow bar 103) and the horizontal arm
108 (and / or
extendable arm 105) may be provided in the clamp 100 and 101 variation, to
allow an
alternative means of quick release. An electrical shutoff switch (not sho -n)
is provided
to both clamp 100 and 101, in case of emergency.
Referring now to Figure 12, a belt 130 variation of attachment means to the
chest wall of the patient 20 is shown wherein patient 20 is (in this case)
sitting upright in
Fowler's position (emergency use of IV's, nasal prongs and monitoring
equipment
according to the preferred embodiment is not shown). Belt 130 is comprised of
semi-
flexible poly-carbonate plastic, selectable in various curves to acconunodate
varying
sizes of chest for patient 20. The polycarbonate material may optionally be
transparent.
Alternatively, belt 130 may be comprised of any other flexible material, which
is highly
resistant to longitudinal strain (such as reinforced leather, nylon or vinyl).
Belt 130 is
adapted to overly substantially flat central panel 132, which is made light-
weight and
stiff in material and design. Central panel 132 is located to match an area on
the chest of
patient 20 over the stemum. Central panel 132 is provided in various sizes to
accommodate different chest wall dimensions and will optimally cover the 2nd
to 6th
intercostal spaces of the patient 20. The distal, cone shaped, active end of
housing 14 of
vibrator 10 is attached and stabilized through slit 133 within central panel
132, having
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CA 02540439 2006-01-27
WO 2005/023121 PCT/CA2004/001621
sides defined by a series of holes with semicircular edges, such that the
vibrating
attachment surfaces of contact or contacts 12 of vibrator 10 make contact widi
the target
site or sites (not shown in Figure 12) on the patient 20. Slit 133 within
central panel 132
has beveled edges (not shown) which taper inwards towards patient 20 to match
the
beveled distal active surface of the conical head of housing 14 of vibrator
10. Central
panel 132, by means of the operator selecting the appropriate location in slit
133, will
allow for variable placement of housing 14 of vibrator 10 and contact or
contacts 12 to
differing intercostal spaces according to the optimal placement established bv
the
operator (according to the methods described earlier). Belt 130 covers the
central panel
132 and partially encircles the torso of the patient 20 such that the ends of
belt 130
extend up to and not beyond the front side of the mid-axial line of the
patient 20 (or, in
other words, up to and not beyond the anterior half of the torso of patient
20).
Altematively, in the flexible belt 130 variations, belt 130 is preferably
longer and is
adapted to substantially encircle the torso of the patient 20. Central panel
132 further
includes a means of securing vibrator 10 comprising slide-able and insert-able
bolts (not
shown) adapted to snap into corresponding slots (not shown) located at the
distal, active
end of housing 14 to thereby lock vibrator 10 in place. Belt 130 further
comprises
matching (but slightly larger) belt slit 13 -i to slit 133 in central panel
132, to further
cradle the beveled distal active end of the housing 14 of vibrator 10, such
that the
proximal, non active end of housing 14 is projected away from the patient 20.
The
securement means of belt 130 to the backside of the patient 20 is enabled
through
utilization of a bungee cord (not shown), which is selectable in varying
lengths and
diameters. The provided bungee cords have ends comprising metal hooks, which
are
made securable to reinforced holes (not shown) placed near the ends of belt
130.
Optionally, the securenient means of belt 130 may comprise any highly elastic
material
which allows for an appropriate degree of strain and recoil under load, in
order to allow
for expansion of the chest of the patient 20 during inspiration while still
maintaining
adequate tension to belt 130 and thereby maintaining adequate engagement force
(i.e. at
least 5-10 N, preferably 20 - 100 N, and optimally 50 - 100 N) to central
panel 132 (and
thereby vibrator 10) to enable the application of vibration therapy regardless
of phase of
respiration of the patient 20. Fine tuning of the engagement force to the
chest wall of
patient 20 is provided to the operator by an inflatable bladder (not shown)
which is
removably placed (while deflated) to the underside of the securement means of
belt 130,
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA2004/001621
preferably to the hollow between the shoulder blades of the patient 20 once
the bungee
cord securement (or variation thereof) is secured in place. The operator
(which may in
this case be or include the patient 20) incrementally inflates (or deflates)
the inflatable
bladder until the desired enga;ement force of vibrator 10 to the chest wall of
patient 20
is achieved (i.e. about 10 - 20 N, and preferably about 20 N in expirarion,
and less than
or equal to about 100 N in inspiration).
A force meter (not shown) is also optionally provided to determine and monitor
engagement force of contact or contacts 12 against the chest wall (or other
body part) of
the patient 20. The maximum engagement force tolerable to the patient 20 is
recommended, so long as vibrator 10 does not dampen (or stop) its oscillations
from too
great an engagement force, and the patient 20 can breathe freely, and tolerate
the
vibration therapy within a detetmined or predetermined safety limit). Belt 130
once
secured with adequate tension, will provide appropriate engagement force to
central
panel 132, which in turn supplies appropriate engagement force to vibrator 10,
(and
contact or contacts 121 - not shown in Figure 12) to enable the application of
vibration
therapy to the chest wall of the patient 20, or altematively the backside or
any body part
of patient 20. The design of belt 130 is advantageous as the patient 20 when
nauseous
may sit up or roll over during vibration therapy.
Variant securement means of belt 130 to the backside (or contra lateral
untreated side) of the patient 20 is obtained by a resilient, substantially
inelastic pair of
VelcroTM straps (not shown), but may as a fnrther variant comprise a pair of
like
securement straps with holes connected by a tang (not shown), or as a further
option a
pair of securement straps connected by a tightenable friction buckle (not
shown). In this
resilient, substantially inelastic variant securement system (which is
preferable for body
parts which do not substantially change size or shape), the same bladder,
(which has a
izreater length than the securement strap's width) is removably centered to
the underside
of the secured inelastic straps, once the straps are fastened. Again placement
of the
bladder is preferably to the hollow of the back between the shoulder blades of
the
patient 20 for chest wall applications, or to the contra lateral (or
diametrically opposed)
untreated side to the body part treated. In addition to the provision of a
control means
for engagement force, the bladder (which is made of a semi conipliant
material), will
buckle slightly at the securement site while under load hence providing a
degee of
compliance to the otlierwise substantially non yielding variant securement
means which
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CA 02540439 2006-01-27
WO 211115/1123121 PCT/CA2004/001621
(unlike the preferred bungee cord rubber securement means) is highly resistant
to
longitudinal strain, thereby enabling the chest of the patient 20 to ex-pand
and relax with
respiration in transthoracic applications. The advantase to the VelcroTM
straps variant
securement system, wlule less compliant and thus offering less comfort to the
patient 20
during inspiration in transthoracic applications, is that it provides for the
most stable
platform to central panel 132 for engagement of vibrator 10 to the chest wall
(or any
other body part treated).
Other variations to the engagement system of belt 130 such as a halter, strap,
sling or vest (i.e. for sitting up or ambulation), may be adapted to the
present invention
by those skilled in the art of vibration or percussion -arment manufacture, to
enable
support and necessary engagement force for the relatively high amplitude
vibration
therapy to be applied to the anterior chest wall of the patient 20 while in an
upright
position. The present invention provides a set of removable, and length
adjustable
shoulder straps (not shown) rhich connect with belt 130 via reinforced
alligator clips,
such as to provide vertical support to belt 130 engagement when the patient 20
is in the
upright position. Alternatively, any other commercially available or adaptable
means of
shoulder strap attachmeni is acceptable. The garment variations will allow
fixation of
vibrator 10 (or provided variant) to the tareet site upon the anterior region
of the chest
wall (i.e. overlying the mediasteinal cavity), while allowing patient 20
movement or
even ambulation during vibration therapy.
It should be understood that the above described variation of engagement means
for belt 130 (and all variations thereof) can be utilized or adapted for any
body part, and
not just to provide engagement to the thorax of the patient 20, and may also
be adapted
to provide support to other suitable vibrators (or percussion instruments by
other name),
and not just the preferred vibrator 10 (or provided variations thereof).
Mobile, Emergency Response System for Paramedic Use:
For first line response by paramedics in an ambulance or before
transportation, a
self-contained, mobile, emergency, response kit for the treatment of acute,
thrombotic
and / or vasospastic vascular obstructions, including a selection of drugs,
drug delivery
supplies, and the preferred vibrator 10 (with a selection of attachment
interfaces to
enhance vibration transmission and effectiveness) is provided. The mobile,
emergency
response kit may also be employed by nurses and / or physicians in the
Emergency
room, upon arrival of the patient 20 to hospital. The preferred application is
for acute
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CA 02540439 2006-01-27
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coronary vascular obstructions, yielding a diagnosis of Acute ST elevation
Myocardial
Infarction.
The mobile, emergency response kit includes:
Vibrator 10 (with bifurcated connector 13 and a set of removably attached
contacts 12 of
varying size),
a) Portable, compartmentalized storage carrying case,
b) Drugs,
c) Drug delivery supplies,
d) Portable high powered DC battery pack, (operational with vibrator 10),
e) A pair of sleeves 23 (each sleeve 23 incorporating an additional pair of
support arms 22) for optional.attachment to bifurcated connector 13,
f) Variant Connector 19 with a pair of variant sleeves 27,
g) Variant non bifurcated connector,
h) Variant ultrasonographic imaging contact 60, and portable ultrasonic
imaging device plus ultrasonic conducting gel,
i) X'ylocaine 2% (for optional freezing of the skin surface treated), and
j) A set of instructions indicating method of use.
Optional provisions for the mobile, emergency response kit include:
a) Clamp 100 (engagetnent means),
b) Variant clamp 101 (engagement means),
c) Belt 130 system (engagement means),
d) Variant LFUS treatment contacts with variant bifurcated connector and
LFUS control apparatus,
e) Variant ultrasonographic imaging and LFUS treatment contact with
LFUS control apparatus,
f) Variant peripheral contact heads with semi malleable attachment
interface,
g) Cardiac phase controlled vibration delivery system comprising; variant
cardiac phase controlled vibrator 11 ("variant 1"), ECG monitorino
system 36, variant processor 35, display monitor 52, variant interface
51, and external accelerometer 39,
h) Variant research vibrator ("variant 2"),
i) Variant light weight vibrator ("variant 3"),
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j) Variant heavy duty vibrator ("variant 4"),
k) Larger, portable, compartmentalized storage canying case, and
1) Set of helmet attachment means comprising helmets of various sizes.
The preferred vibrator 10 for the mobile, emergency response kit is operable
to
emit vibration within the 1 - 120 Hz range, and provides a selection of
displacement
wave fomi emissions (i.e. sinusoidal, square, saw tooth, and exponential
waves), with a
masimum displacement amplitude of up to 15mm. Vibrator 10 is operational under
engagement forces of up to about 100 N, such as to enable a high energy,
deeply
penetrating emergency system of vibration therapy. Vibrator 10 runs on AC
power via a
power cord, or alternatively by battery power via a high powered removable and
interchangeable DC battery pack.
The variant research vibrator ("variant 2") is of optional inclusion to the
mobile
emergency response kit, and offers a higher range of vibration frequencies
within the
range of 1 - 1000 Hz. The variant research vibrator ("variant 2") has a
Iiniited
displacement amplitude enablement (i.e. in the low millimeter to sub
millimeter ranges)
and is primarily used for research purposes (i.e. in the 150 - 1000 Hz range)
and / or use
with variant ultrasonographic imaaing contact 60 for directed vibration
therapy. Also,
the variant light weight vibrator ("variant 3"), and the variant heavy duty
vibrator
("variant 4"), are both optionally included. The variant heavy duty vibrator
is
particularly effective in cases where high engagement forces are required to
ensure
therapeutic penetration, such as when the patient 20 is obese, or when the
upper back (or
posterior thoracic region) of patient 20 is utilized as an application site
(as described
earlier). The variant light weight vibrator ("variant 3") is preferable if the
patient 20 is
utilized to engage the device, or self administer the vibration application.
The mobile, emergency response system comprises a self contained system,
employing a module and portable storage carrying case (not shown) which houses
the
components of the mobile emergency response kit. A variant larger portable
storage
carrying case (not shown) is adapted to additionally house optional
components.
The mobile, emergency response system enables systemic dru- delivery, via
intravenous, intra arterial, subcutaneous, oral, topical and nasal drug
administration
means. Drugs within the mobile, emergency response kit include: thrombolytic
agents
(e.g. ACTIVASET"' (Alteplase), TNKaseTM (Tenecteplase), RETAVASETM
(Reteplase),
AbbokinaseTM (Urokinase), ItiabikinaseTM (Streptokinase with water),
StreptaseT"'
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CA 02540439 2006-01-27
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(Streptokinase with 0.9% NaCI solution), Lanoteplase); GP 2b 3a platelet
inhibitors (e.g.
ReoProTM (Abciximab), AGGRASTATT`t (Tirofiban hydrochloride), IntegelinTM
(Eptifibatide)); calcium channel blockers (e.g. ISOPTINT"' SR (Verapamil HCl),
ADALAT YI.T" (Nifedipine), CardizeniTM (Diltiazem), NORV_ASCTM (Amiodipine
besylate); Nitrates (Nitroglycerine (spray, pill or patch), isosorbide
dinitrates (IsordilT'"
and SorbitrateTM), NiprideTM (Nitroprusside); Oral anti-platelets (e.g.
Acetylsalicylic
Acid (Aspirin), PlavitiTM (Clopidogrel), TICLIDTM (Ticlopidine hydrochloride);
Anti-
coagulants such as heparin; and concentrated oxygen. It should be understood
that the
mobile eniergency response kit may contain any one of the above listed drugs,
or any
nunlber of the above listed drugs in any combination.
Non-pharmacological "drugs" such as echo contrast ajents (i:e. micro bubble
solutions which lower the cavitational threshold of a niedium), which may be
delivered
systemically along with other IV drugs, are optionally included in the mobile,
emergency response kit to enhance the agitative internal effects of externally
delivered
vibration therapy. Optional cavitating micro bubble solutions within the
mobile,
emergency response kit include: EchoGenTM (Dodecafluoropentane emulsion),
A.lbunexTM (5% human albumin), LEVOVISTTM (Galactose Palmitic Acid ultrasound
contrast auent). Air containing albumin microcapsules (QuantisonT," and
VlyomapTM),
SonoVueTM (Sulfurhesafluoride) and Perfluorocarbon containing microbubbles
(Perfluorocarbon exposed sonicated dextrose albumin PESDA). Cavitating
microbubbles solutions are particularly effective in conjunction with joint
LFUS
administration, and are readily implemented in conjunction with use of the
variant LFUS
treatment contacts, or variant ultrasonographic imaging and LFUS treatment
contact, as
per the "dual therapy" or "multifunction system" niethods of LFUS
administration as
described earlier.
Drug delivery supplies within the mobile, emergency response kit include: N
tubing, IV start kits, sterile IV introduction needles, tape, IV pole, 0.9
NaCI IV
solutions, Dextrose N solutions, Code 8 IV solutions, Heparinized IV
solutions, N
pressure bag with pressure gauge and pressure bulb, sterile intra arterial
introduction
needles, guide wires, sheaths with dilators, scalpel blades, one way
stopcocks, three way
stop cocks, sterile drapes, sterile gowns, sterile ggloves, sterile skin
preparation solution,
needles adapted to subcutaneous drug delivery, alcohol swabs, paper cups,
straws,
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sublingual sprays, aerosol sprays, oxygen tank, ambubag, oxygen tubing, oxygen
mask, and
nasal prongs. It should be understood that the mobile emergency response kit
may include any
one of the above listed drug delivery supplies, or any number of the above
listed drug delivery
supplies in any combination.
The variant ultrasonographic imaging contact 60 (with a portable hand carried
ultrasonic imaging device-not shown), is also provided to the mobile,
emergency response kit,
so a skilled operator (when available) can optionally establish a viable sonic
penetration
window and target the culprit vascular region (directly or by anatomic
reference) with low
frequency vibration with optimal efficiency. Variant ultrasonographic imaging
contact 60 is
readily adaptable for use in all provided variations of vibrator 10 (i. e. as
per the "optional
provisions" listed above), and is of preferred use when a trained operator is
available, and
with the variant research vibrator ("variant 2"), whereby a directed approach
for higher
frequency lower displacement atnplitude vibration (i. e. above 150 Hz) is
generally required
to ensure therapeutic levels of penetration to the culprit region targeted.
The variant ultrasonographic imaging and LFUS treatment contact is also
optionally
provided to the mobile, emergency response kit to enable the application of
ultrasonic
iniaging, low frequency vibration, and low frequency ultrasound (as a second
therapeutic
wave form) simultaneously and in concert via the tnultifunction system (as
previously
described). For cost effectiveness, a pair of variant LFUS treatment contacts
(with variant
bifurcated connector), enabling einissions of low frequency ultrasound without
imaging
capabilities (i. e. without the use of a relatively expensive incorporated
ultrasound imaging
'transducer-as per the "dual therapy" option) is also optionally provided.
1'he IV or IA
administration of cavitating microbubbles, with or without other helpful drug
agents (e. g. as
per the methods disclosed in US 5,695, 460) are recommended as an adjunct low
frequency
vibration and joint LFUS wave form delivery.
The cardiac phase controlled vibration delivery system is optionally included
within
the mobile, emergency response kit for treatment of Acute Myocardial
Infarction complicated
by cardiogenic shock. A cardiac phase "mode" selection enables cardiac phase
dependent
vibration delivery, wherein "mode" defines the timing of emission of vibration
therapy
according to cardiac phase (i. e. systole vs. diastole). The selection of
vibration mode enables
the application of vibration specifically during the diastolic
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phase of the cardiac cycle, which is useful in AivII cases which have
deteriorated to
cardiogenic shock as diastolic vibration, besides agitating and assisting
dissolution of
the culprit coronary obstruction, is also known to provide a positive
inotropic effect.
The provided cardiac phase dependent vibration delivery system is optionally
programmable to enable the selection of varying frequency of vibration
according to
cardiac phase. It is advantageous to for example vibrate the myocardiuni
between 20 -
60 Hz (and optinially 50 Hz) during ventricular diastole (approximating the
diastolic
resonance frequency of the myocardium) and to vibrate the myocardium between
70 -
120 Hz (and optimally 100 Hz) during ventricular systole (thereby
approximating the
systolic resonance frequency of the myocardium which is stiffer in systole).
Higher
frequencies at same displacenient amplitude are generally laiown to improve
blood clot
disruption and induce cavitation and acoustic streaming, thus taking advantage
of the
myocardium's higher vibration resonance frequency during the systolic period
(or
debatably at any time throughout the cardiac cycle) is advantageous.
For the sake of simplicity and ease of portability, the mobile, emergency
response kit of the present invention incorporates only the mandatory elements
to enable
the aforementioned cardiac phase controlled vibration delivery system wherein
ECG 36,
variant processor 35, variant interface 51, display monitor 52, external
accelerometer 39,
and variant cardiac phase controlled vibrator 11 ("variant 1"), is all that is
utilized to
enable cardiac phase controlled vibration delivery. The deflection of the QRS
complex
from ECG 36 is interpreted by variant processor 35 (which defines the timing
of the
onset of "ventricular systole"), and a rate related timing delay is thereafter
applied
following the QRS complex (which defines the timing of the onset of
"ventricular
diastole"). Variant processor 35 is thereby enabled to respond to operator
inputted
cardiac phase modulated vibration algorithms and therein provide output
commands to
variant cardiac phase controlled vibrator 11 ("variant 1"), to enable the
delivery of
cardiac phase dependent tinle and optionally frequency varying vibration
therapy. The
operator, upon viewing the ECG 36 and accelerometer 39 output on the display
monitor
52, can adjust (or fine tune) the timing of vibration emission via the variant
interface 51.
Ideally dia'stolic vibration should commence from the terminal end of the T
wave, and
then discontinue upon the onset of the deflection of the QRS complex as
visualized by
the provided ECG 36 wave form. As stated the use of the "advanced method" is
of
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significant importance when the patient 20 is suffering from an acute coronary
vascular
obstruction which has deteriorated to a state of cardiogenic shock.
In a variation, the variant cardiac phase controlled vibrator 11 may be
adapted to
provide a self contained operator held unit (i.e. complete with control means,
processing
means, display means, cardiac phase nionitoring means, and vibration timing
indication
means - as described earlier), such as to enable a more easily portable and
expedited
cardiac phase controlled vibration delivery system to the mobile, emergency
response
kit.
Further options to the mobile, emergency response kit include an engagement
means (i.e. clamp 100 or clamp 101, and/ or belt 130 system) so that an
operator need
not hold vibrator 10 (or provided variant) by hand throughout the course of
vibration
therapy. A retractable IV stand (not shown) is optionally incorporated within
and
extending from bar 106 of clamp 100. In another variation of clamp engagement,
bar
106 (i.e. in clamp 100) and I or hollow bar 103 (i.e. in clamp 101) may be
placed and
supported directly to the stretcher of the patient 20 by a vice grip or other
locking
mechanism (i.e. rather than to base 102), or, arm 108 (i.e. in clamp 100) and
/ or
extendable arm 105 (i.e. in clamp 101) may be alternatively supported by a
portable unit
with lockable wheels or directly to a wall or fixture in the emergency room or
within the
ambulance.
It should be understood that while the mobile, emergency response lcit
advantageously employs the preferred vibrator 10 (such as to enable a high
degree of
operator enabled vibration emission control), this employment (or choice of
vibrator 10)
is not critical in the mobile, emergency response system and alternatively any
known (or
adaptable) low frequency (i.e. operational in the 1- 120 Hz range) vibrator
(or
percussion, or oscillation device by other name), with a suitable attachment
interface for
selected body surface contact (preferably enabling concentrated delivery of
vibration
between the rib space or spaces of the patient 20), being operable at high
displacement
amplitudes (i.e. > 2 mm, and preferably > 4 mm deflections) and engagement
forces (i.e.
> 5- 10 Newtons, and preferably > 20 Newtons), niay alternatively be used,
regardless of
the level of operator enabled vibration control.
It should similarly be understood that cardiac phase controlled vibration
delivery
according to the mobile, emergency response system may be embodied (by
apparatus) in
many ways, and should not be restricted to the system herein described. Any
low
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frequency vibrator (or vibration system), preferably operable at a high
displacement
amplitude (i.e. greater than2 mm and preferably greater than 4 mm deflections)
and high
engagement forces (i.e. at least 5-10 N, and preferably greater than 201 t),
which is
adapted to provide cardiac phase controlled vibration delivery (i.e. with
vibration timing
emission algorithms and optionally vibration frequency algorithms) may be
used. The
apparatus may comprise a plurality of separately located elements (as
provided), or may
alternatively comprise a single, self contained operator held instrument (as
described
earlier).
Furthermore, while the preferred emergency response kit (or drug delivery
system by other name) advantageously comprises a plurality of useful and
interrelated
components (such as to optimally enable function of the apparatus, regardless
of the
skill level of an operator), it'should be understood that all that is
ultimately required is a
suitable low frequency vibration device (as described above), plus any one (or
combination) of the aforementioned listed members, according to the invention.
Referring now to Figure 13, the preferred method of employment of the vibrator
10 (or percussion device by other name) for treatment of acute vascular
obstructions is
schematically shown. Step (A) comprises the step of systemically
administrating at least
one and preferably a plurality of useful drugs adapted for treatment of an
acute vascular
obstruction which is usually a combination of thromboses and vessel spasm.
Such drugs
may include but not be limited to thrombolytics, GP 2b 3a platelet inhibitors,
nitrates,
anti coagulants, oral anti-platelets, concentrated oxygen and morphine. Step
(B)
comprises the step of applying vibration to a selected or pre-deterniined
external body
surface deemed proximate the acute vascular obstruction via the preferred
vibrator 10
(or other suitable percussion device as described above). Application by
vibrator 10 is
preferred in the case where the operator has no specialized skill or training
in ultrasonic
imaging (which would be the most common scenario in the field or in the ER).
Engagement to the anterior chest wall bridging the stemum is shown (which is
preferred
in acute myocardial infarction cases, although the backside of the patient and
other areas
upon the chest wall may also be utilized), and ideally the highest force or
displacement
amplitude deemed safe and tolerable to the patient 20 is selected to ensure
optimal
penetration and effectiveness of the percussive signal. Step (D) comprises the
provisional step of employing diastolic timed vibration via the cardiac phase
controlled
vibration delivery system (or any suitable variation thereof) in the special
case wherein
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the patient 20 deteriorates into a state of cardiogenic shock or cardiac
failure, which is
not uncommon in acute myocardial infarction cases. Diastolic timed vibration
is known
to reduce LV diastolic pressures and promote a positive inotropic effect to LV
function.
Otherwise "continuous" vibration may be continued or discontinued in
accordance to a
risk / benefit decision by a responsible operator. It should be understood
that the
initiation of vibration (B) may proceed or be concurrent with the
administration of drug
therapy (A). Furthermore, it should also be understood that vibration therapy
(B) may
alternatively be utilized alone without adjunctive drag therapy (A), such as
in the special
cases whereby drug therapy is not indicated (i.e. for patients with
substantial bleeding
risks or other co-morbid factors), drug therapy is not available (i.e. at home
or in the
field), wherein drug therapy is not allowed or not authorized (e.g. patient
refusal, or in
the case where the operator is not authorized to give drugs), and / or wherein
drug
therapy is not preferred or not prescribed.
In reference to Figure 14, a variation to the preferred vibration method
incorporating the employment of ultrasonic imaging to direct vibration is
shown. Step
(A) comprises the same step of systemically administrating a clot dissolving
and / or
vasodilatory drug to the patient 20 as per the prescribed therapy. Step (C)
comprises the
step of applying and directing vibration by means of ultrasonic imaging (i.e.
the variant
dual function imaging vibration device 15 applied to patient 20 is shown,
however any
suitable vibrator - as described above - coupled to an ultrasonic imaging
transducer at its
active end may be used). The variant dual function imaging vibration device 15
(or
variation thereof) is optimally placed and directed via ultrasonic imaging, to
emit
vibration towards an acute vascular obstruction targeted. This is accomplished
by either
direct visualization (e.g. such as visualization of a blood clot within a
blood vessel) or
by anatomic reference, wherein for example placement in pro:timity to the base
of the
heart, and visualization of the substantialIy akinetic, basal aspect of the
myocardium
wherein the culprit blood clot is Iikely to reside defines preferred placement
and
direction of vibration in acute myocardial infarction cases. Step (D)
comprises the
optional step of employing diastolic timed vibration via the cardiac phase
controlled
vibration delivery system (or suitable variation thereof) in the special case
vvherein the
patient 20 deteriorates into a state of cardiogenic shock or cardiac failure.
Again it
should be understood that vibration therapy directed by ultrasonic imaging (C)
may be
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independent of drug therapy (A), and may alternatively proceed or be initiated
concurrently with the iniriation of drug therapy (A).
In reference to the application of the mobile eniergency response kit in the
field,
a tutored paramedic or physician, once arriving to the patient 20 and
establishing a
diagnosis, preferably selects at least one drug based upon clinical need and /
or patient
20 bleeding risks, systemically adniinisters the drug (or drugs), and then
transcutaneously vibrates the body surface of the patient 20 deemed to overly
the
general area of the acute culprit vascular obstruction. As stated a skilled
imaging
approach to direct vibration may be employed if the operator has the skill and
training
required to recognize pertinent ultrasonic images, otherwise the preferred
vibrator 10 (or
other suitable non-imaging vibrator) with a pair or optionally a plurality
beyond a pair of
contacts 12 should be utilized. Low frequency vibration in the sonic to
infrasonic ranges
(i.e. 1- 120 Hz; preferably 20 - 120 Hz in cardiac applications), or at any
frequency
within the 1-1000 Hz range may be used. Generally, the default frequency of 50
Hz
sinusoidal vibration is preferred, as 50 Hz sinusoidal vibration can be
delivered at a
relatively high displacement amplitude, has excellent penetration
characteristics through
the chest wall and other body surfaces, falls within the resonance frequency
of the heart,
and is a well established frequency known to produce vascular dilation,
cavitation, and
acoustic streaming for encouraged clot disruption and increased drug mixing
and
permeation. Altematively, square wave <b> (i.e. with a steep displacement rise
for high
impact, better penetration and disruptive action), saw tooth wave <c>,
exponential wave
<d> or any linear or nonlinear (or combination thereof) displacement wave
form, may be
used (see Figure 8). Generally the maximum tolerable (and judged safe) force
or
displacement amplitude should be utilized in cases of acute myocardial
infarction or
acute vascular obstructions to the pulnionary or peripheral vasculature,
wherein cell
death, and / or hemodynamic comproniise is otherwise inuninent. A gentle 1- 2
mm
displacement amplitude may be preferable for the treatment of ischemic stroke
(preferably via application of the contacts 12 of vibrator 10 to the
posterior, posterior
lateral or lateral aspect of the neck of the patient 20 or via the provided
helmet
attachment means) until a definite diagnosis of ischeniic (or embolic) stroke
is
established, however higher treatment amplitudes may be considered as first
line
treatment according to a risk / benefit weighted decision (i.e. risk of
cerebral
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hemorrhage vs. benefit of accelerated reperfusion) made by the attending
clinician, or
after the diagnosis of embolic stroke (i.e. vs. hemorrhagic) is established.
The patient 20 is transported to hospital or other treatment facility,
preferably
with vibration and drugs simultaneously delivered. The vibration therapy
preferably
continues until clinical signs of reperfasion are evident, or until an
invasive corrective
procedure such as emergency PCI (i.e. in heart attack cases) is established.
Portable, Emergency Response System for Outpatient Use:
For first line treatment of a citizen in the community (e.g. before the
arrival of
paramedics), a self-contained, portable, emergency response I.-it for the
treatment of an
acute thrombotic coronary vascular obstruction at early stage is provided.
Components
of the portable emergency response kit include the variant liglitweight
vibrator ("variant
3"), and preferably at least one anti anginal medication to be delivered. The
portable,
emergency response kit is designed to be utilized by the patient 20 as an
emergency tool
for self administration (or assisted administration by a non-trained or
indeterminately
trained bystander) within the conununity.
The portable, emergency response Icit comprises a black leather portable
carrying case which is adapted to house and port: the variant lightweight
vibrator
<"variant 3"> (including bifurcated connector 13 with a set of removably
attached
contacts 12 of various sizes), a portable DC power pack, an AC power cord,
preferably
at least one anti-anginal medication (such as Nitro spray, Nitro pill, Nitro
patch,
IsordilTM, and/ or SorbitateTM), and optimally at least one oral antiplatelet
medication
(such as Acetylsalicylic Acid, Plaviu:T"', and/ or TICLID). A larger brown
leather
carrying case is adapted to additionally house and port a small oxygen
canister and nasal
prongs to enable the administration of concentrated oxygen to the patient 20,
as well as a
small portable blood pressure device adapted to take blood pressure from the
wrist of
patient 20. The belt 130 engagement system (i.e. with inflatable bladder,
bungee cord
securement and, shoulder strap support - described earlier) may be provided so
the
patient 20 need not hold the unit by hand during the course of therapy. The
patient 20 is
instructed to carry a cellular phone at all times to enable calling for
emergency
assistance when necessary. The use of the variant lightweight vibrator
("varian t 3") is
preferable in the portable emergency response system as the unit is light
weight and easy
to "self' apply by the patient 20. As an option, the preferred vibrator 10 or
variant
heavy weight vibrator ("variant 4") may be altematively selected, or any other
low
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frequency commercially available vibrator (preferably offering vibration
displacement
amplitudes of greater than at least 2 mm) may be used according to the
preference of the
patient 20.
Vibration therapy is, in this case, employed for acute states of coronary
insufficiency with symptoms consistent with infarction refractory to
nitroglycerine
treatment in the patient 20, wherein an acute coronary thrombotic obstruction
(i.e.
"Heart Attack") cannot be ruled out. Every bout of chest discomfort that the
patient 20
in the community experiences might in fact be an acute coronary event wherein
a plaque
has ruptured and an acute thrombotic vascular obstruction has occurred.
The method of use of the portable emergency response system and lcit comprises
maintaining the portable emergency response kit in proximity of the patient 20
at all
times. When a symptom of "angina" is felt by the patient 20 (i.e. chest pain
or pressure,
shortness of breath, nausea, diaphoresis, or "an impending sensation of
doom"), patient
should undertake anti-anginal medical therapy as prescribed by his or her
physician.
15 In these cases, the patient 20 will try the prescribed anti-anginal
medication such as nitro
spray x 3 (i.e. with each dose spread 5 minutes apart), and upon recognition
of no relief
of chest discomfort (which may be quite severe), patient 20 will proceed to
dial "911
wherein the diagnosis of an acute coronary thrombotic obstruction leading to
an acute
MI cannot be ruled oiit until a professional diagnosis is obtained. As
described earlier,
20 hyper acute early clot formation at early stage is extremely amenable to
dissolution via
mechanical agitation, hence a mechanically disruptive, agitative technique
such as the
application of high amplitude chest wall vibration therapy as herein
described, is
prospectively an extremely effective and important first line emergency method
and tool.
The patient 20 will rest and preferably additionally administer an oral
antiplatelet
medication (as above) as prescribed by a family physician or Cardiologist of
the patient
20. The patient 20 should articulate the potential medical problem of a
potential "heart
attack" to bystanders such that patient 20 is not alone while waiting for the
arrival of an
ambulance and professional care (i.e. in the case of cardiac arrest). The
variant
lightweight vibrator ("variant 3"), or other selected vibrator is placed to
the anterior
chest wall preferably to bridge the sternum at the default level of the fourth
intercostal
space (although other attachment configurations are possible as per the
methods
described earlier). The blood pressure of the patient 20 may be monitored via
the small
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portable blood pressure device, and oxygen may be administered until
professional
assistance arrives.
The chest wall interface of the variant lightweight vibrator ("variant 3") is
advantageously accomplished via the bifurcated connector 13, preferably
equipped with
preferably a pair of pre sized contacts 12, wherein the contacts 12 have been
pre
adjusted in location on support arms 22 to optimally bridge the stemum and
seat within
the intercostal spaces of the patient 20 for maximum chest wall penetrability
to the
coronary circulation as per the methods previously described. Optionally,
variant
connector 19 disposing two pairs of support arms 22 (to enable four
application sites via
four contacts 12 to the patient 20) , or bifurcated connector 13 disposing an
additional
two pairs of support amis 22 (to enable a total of three pairs of application
sites via three
pairs of contacts 12 to the patient 20) may be utilized for multiple
intercostal space
attachnlent, to enable maximal penetration of low frequency vibration to the
deeply
situated and variably located cardiovascular regions within the thoracic
cavity.
The vibration displacement amplitude is preferably selected as the matimum
tolerable to the patient 20, who should ideally be resting in either the
supine position or
seated comfortably in a chair. The optimal frequency is selected at 50 Hz
continuously
applied vibration with a sinusoidal wave fomi, however optionally any
frequency within
the 1- 120 Hz range, or preferably 20 - 120 Hz range (i.e. to match the
resonance
frequency of the heart) and, square, exponential, or saw tooth displacement
wave forms
may be optionally selected according to the preference of the operator and /or
prescribed
therapy. Ideally a friend or bystander should engage the variant lightweight
vibrator
("variant 3"), or other provided vibrator against the patient 20 by hand until
professional
care arrives. Alternatively, belt 130 with shoulder straps (or other variant
garment, as
described earlier) may be utilized, such that the patient 20 can self
administer vibration
therapy without the need to exert any effort to hold the variant lightweight
vibrator
("variant 3"), in place. The patient 20 will preferably administer a dose of
anti anginal
medication such as nitro spray 0.4 mg SL (and optionally an oral anti platelet
agent), and
then proceed to administer adjunctive vibration therapy (as per the methods
disclosed
earlier) such as to provide a synergistic treatment system to assist localized
drug
effectiveness to the coronary vasculature. Monitoring of the blood pressure of
the
patient 20 (i.e. via the optimal small portable blood pressure device) is
advantageous as
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repeated dosing of nitroglycerine (or other nitrate employed) may be
accomplished
barring hypotension during vibration therapy.
As an option, the variant lightweight vibrator ("variant 3"), or other
selected
vibrator, may be adapted to enable cardiac phase controlled vibration via the
incorporation of an ECG monitoring system and suitable processing and control
network
(i.e. as a "self contained unif' - as described earlier), such as to enable
the application of
vibration restricted to the diastolic phase of the cardiac cycle of the
patient 20 wherein it
may be considered useful to provide a therapy which promotes a positive
inotropic
effect whereby the blood pressure and hemodynaniic status of patient 20 may
deteriorate
(or will be unknown) until professional care arrives. The ECG monitoring
system in this
case may advantageously comprise at least a pair of electrodes operatively
incorporated
with or disposed upon at least a pair of contact surfaces of the utilized
vibration
attachment interface (e.g. which may for example comprise the preferred pair
of contacts
12 disposed upon bifurcated connector 13, or a plurality of contacts 12
wherein support
structure 24 is utilized - as described earlier), such as to enable a simple
and easy
application means to the patient 20, without the bother of attaching
electrocardiographic
leads and so fortl-.
It should be understood that while the embodiment shown to the portable
emergency response system (and lcit) advantageously incorporates the variant
lightweight vibrator ("variant 3"), altematively any known (or adaptable) low
frequency
(i.e. 1 - 120 Hz) vibrator (or percussion, or oscillation device by other
name) of size and
shape to enable hand held operation, with a suitable attachment interface for
selected
body surface contact (i.e. preferably enabling concentrated delivery of
vibration between
the rib space or spaces of the patient 20), being operable at high
displacement
amplitudes (i.e. > 2 nun, and preferably > 4 mm deflections) and engagement
forces (i.e.
> 5- 10 Newtons, and preferably > 20 Newtons), may altematively be used. Such
vibration devices should preferably be adapted to portable battery operation,
to enable
the application of vibration therapy in community wherein an AC wall outlet
may not
always be available.
. It is significant that acute coronary thrombotic obstruction in the
community is
one of the leading causes (if not the greatest cause) of death in the
civilized world today.
Many modifications are possible to the emergency system witliout departing
from the spirit or innovative concept of the invention.
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With regards to the vibration source of preferred vibrator 10, while the
embodiment
shown advantageously employs an electromechanical transducer comprising a high
powered
linear stepper motor (such as to enable a high level of vibratory control and
selectivity of
frequency, displacement amplitude and vibratory displacement wave forms),
altematively any
known (or adaptable) low frequency (i, e. 1- 120 Hz) vibrator (or percussion
device, or
oscillation device by otlier nanie), with a suitable attachment interface for
selected body
surface contact (preferably enabling concentrated delivery of vibration
between the rib space
or spaces of the patient 20), being operable at high displacement amplitudes
(i. e. > 2 mni, and
preferably > 4 mm deflections) and engagement forces (i. e. > 5-10 Newtons,
and preferably
> 20 Newtons), may alternatively be used, regardless of the level of operator
enabled
vibration control.
For example, to achieve the same level of vibration control, a lower stroke
length
enabled linear stepper motor (i. e. with a smaller stator tube) in conjunction
with a
displacement amplifier may be used. Linear stepper motors of lower stroke
enablement are
more common and commercially available, hence generally less expensive to
employ.
Alternatively, a high powered rotary stepper motor equipped with an
exchangeable rotary to
linear conversion element, or a specialized rotary to linear conversion
element, (wherein the
conversion eleinent independently or in coticert with the motor operation,
enables adjustable
displaceinent amplitude emission control) may be used. Conversion elements of
this type are
described (for example) in US 6,027, 444 and US 827,133. Furthermore, a rotary
stepper
motor configured to oscillate controllably in an up and back manner along an
arc of less than
or equal to 180 degrees (and preferably less than 120 degrees) in conjunction
with a cam or
crank may be used to take the functional place of the provided "linear"
stepper motor.
Rotary motors are generally less expensive than linear motors. In yet a
further variation, a
ceramic servo motor coupled to a linear stage (as per modem, state of the art
technology
offered by Nanomotion LTD), could be utilized to replace the provided linear
stepper motor,
and provide virtually unlimited linear motion control.
For example, if only selectable displacement amplitude control is required,
the
electroinechanical transducer may comprise any high powered rotary motor
interfaced with a
specialized carn or crank, wherein the cam or crank is exchangeable, or
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independently adapted to enable adjustable displacement amplitude control
(e.g. as per
technology in US patent 6,027,444 or US 827,133 mentioned previously); a high
powered linear motor of any type operational at a predetermined stroke coupled
to a
specialized linear conversion element which is adapted to enable variable
displacement
amplitude control (such as, for example a lever system with an adjustably
located
fulcrum); a ceramic servo motor coupled to a linear stage (as above); or a
linear stepper
motor without the enablement of varying displacement wave shape control.
For example, if only variable displacement wave form control is required, then
any high powered rotary stepper motor with a rotary to linear conversion
element could
be utilized. Altematively, a ceramic servo motor coupled to a rotary stage
(with rotary
to linear conversion element). or a ceramic servo motor coupled to a linear
stage could
be used. Furthermore, in the case high impact "pulsed", or "square wave"
vibration is
desired (i.e. as a sole wave shape with a steep displacement rise per stroke-
for deeper
penetration and superior disruptive action) a technology as per US patent
5,951,501 or
US 6,682,496 may be used, (or any other I.-nown technology), which utilizes a
rotary
motor with a specially engineered cam which is engineered to enable "striking"
of a
contact surface in a percussive manner. It should be noted that if a "pure"
sinusoidal
displacenient wave form is desired (i.e. as a sole wave shape - which has
demonstrated
superior vasodilatation characteristics) a rotary motor (of any type) with a
rotary to
linear conversion element such as a cam or crank may be employed.
For example, if selectable "force" or "power" ofvibration control (i.e. max
force / stroke, and / or force wave shape control) is desired at a given
frequency (as
opposed to exacting displacement amplitude control and / or displacement wave
shape
control); a linear induction motor with adjustable force or power control, a
linear
permanent magnet motor with adjustable force or power control, a linear
stepper motor
with adjustable force or power control, a high powered speaker coil with
adjustable
power or volume control, a shaker with adjustable force or power control, a
ceramic
servo motor coupled to a linear or rotary stage with force or power adjustment
control,
or a plurality of select-ably aligned eccentric spinning weights rotating in
adjustable
relation to one another (as in variable force pile driving technology), may be
used.
Furthermore, a fiuniture item such as a chair or bed containing an adjustable
force and /
or waveform vibrator or vibrators (i.e. for vibration to the backside of the
patient 20,
such as in treatment in acute myocardial cases) may be used as a new
application for a
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known technology. Examples of such vibrating chairs or beds, which necessarily
provide
reciprocating motion in a direction perpendicular to the long axis of the
thoracic cavity and
torso in cardiac applications (such as to enable significant penetration of
the vibratory signal
to the structures within the thoracic cavity) are disclosed in Canadian Patent
Application No.
2430229, PCT Application No. WO 00/67693, and Japanese Utility Model
Application No.
Hei 296 133.
For example, if no (or minimal) vibratory control is desired, then any
commercially
available high powered vibratory massage or percussion system (i. e. providing
greater than 2
mm deflections) operable under reasonable load (i. e. at least 5- 10 N, and
preferably at least
about 20-100 N), such as for example the Mini Pro 2 Thumper, Thumper TM, 1-
lomedics
Professional Percussion Massager model I PA- 1 H, Sharper Image Massager Model
HF 757,
Dr. Scholl's Pulsating Masseur Model DR7591, Dr. Scholl's Twin Turbo TM
Percussion
Massager Model DR7593, Conair Model "hHP1R Professional Percussion Massager,
OSIM
Tappie, OSIM Turbo 2, Dr. Scholl's Full Cushion Massager, Dr. Scholl's
Cushioned Massage
Mat, OSIM iMedic Chair (i.e. for applications to the upper back region), OSIM
ChiroPro (i.e.
for applications to the posterior and lateral aspects of the neck), and the
"deep muscle
stimulator device" as disclosed by Pivaroff in US patent 6,682, 496, may be
used as a new
application for a known technology. These devices (many of which
advantageously comprise,
-or could be easily adapted to provide-a pair of contacts), typically emit one
solitary high
displacernent amplitude stroke without a displacement amplitude regulating
control, hence
control of the applied forces to the body surface treated (to tailor the
intensity of the
application to suit the tolerance level of the patient 20), may be achieved
via use of a cloth or
cushion (i. e. to dampen application forces) or via a modulation of the
engagement force
applied to the vibrator against the application site. Such vibrators, (all of
which tend to run
exclusively on AC power cord), may be preferably (and easily) adapted by those
skilled in the
art of vibration device manufacture for portable battery operation to enable
use in the field (or
community), wherein no AC wall outlet may be available.
Also, while the preferred embodiment (apparatus) discloses a single motor
located
within housing 14 of vibrator 10, a pair or a plurality beyotid a pair of
motors may also be
used (for example, one motor for each contact 12).
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It should also be noted that there is effectively no definable maximal nor
minimal
limit to displacement amplitude or engagement force applied in emergency
vibration therapy
(i.e. the intensity emitted is generally a function of the tolerance of the
patient 20 which will
vary markedly). Any of the above variations to vibration source may be
therefore adapted in
size and scale to enable vibration at higher or conversely lower loads and
displacement
amplitudes than what is otherwise disclosed according to the invention. For
example, while
the preferred etnbodiment shown (i. e. vibrator 10) provides a peak
displacement amplitude of
up to 15 mm, this enablement is generally in excess of what is typically
required, and a device
limited to lower peak displacement amplitudes (i. e. with an upper limit as
low as about 4-8
mm), may alternatively be employed for satisfactory results. Lower peak
displacement
amplitude devices are potentially "safer" (i.e. as the" tolerance" level of
the patient 20 may be
difficult to judge at the time of treatment), and confer lighter weight more
compact systems,
which are generally easier to maneuver and operate by hand. In an exemplary
alternative
embodiment, the vibrator employed may be operable to the maximum displacement
amplitudes allowable (i. e. deemed safe) under the officiating governmental
regulatory body
or bodies of the country wherein the vibrator is to be commercialized.
With regards to the preferred attachment interface, while the einbodiment
shown
incorporates shaft 16 projected away from housing 14 for transmission of
vibration to contact,
or preferably, contacts 12 to the patient 20, shaft 16 is not an essential
component of vibrator
10 (or provided variant), and any transniission piece, or even the attachment
interface itself,
may be operatively linked directly to the active end of the electromechanical
transducer
within housing 14 of vibrator 10 (or variant). An attachment design like that
of Homedics
Model PA-l00 massager (which incorporates a pair of electronically adjustably
spaced
vibration heads intimately mounted through the active end of the housing of
the vibration
device) is an exemplary alternative. Also, any of the aforementioned
variations to contact 12
attachment (including suction cups, a single contact 12, a plurality beyond a
pair of contacts
12, and variant contacts enabling ultrasonic imaging and/or LFUS wave form
emissions) may
be utilized solely, or in any combination, as per the methods described, to
best suit the clinical
situation and/or preference of the operator.
In yet another possible embodiment of attachment, the preferred contacts 12
may be
replaced by a resilient nondistortable container filled with a substantially
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incompressible fluid overlain with a serni-compliant membrane (i. e. of size
and shape such as
to enable bridging of the sternum), wherein the vibration emitted from the
active components
of vibrator 10 (or variant) may be transmitted through the incompressible
fluid and membrane
and thereafter to the patient 20. The sem_i-coinpl_iant membrane (which
cornprises the patient
20 tissue interface) is highly resistant to longituditial strain hence
conservation of volume is
achieved and vibration is efficiently transmitted. This arrangement (which
enables an exacting
contoured fit to the body surface treated) offers a potentially more
comfortable application to
the patient 20.
The engagement of the utilized vibrator (or percussion device by other name)
to the
selected body surface of the patient 20 may be varied in many ways. While the
embodiments
shown comprises use of the hand (s) of an operator, clamp 100 or 101 or belt
130 (and
variations thereof), alternatively the employed vibration source may be
engaged by means of
an upper back support of a chair (e. g. such as in the OSIM iMedic Chair), or
stretcher (or
table), wherein the selected vibrator (or percussion instrument) is housed and
preferably
nianeuverable within or through the upholstery of the supportive unit.
It is also possible to utilize more than one vibration device for placernent
to a
plurality of locations along the body of the patient 20, such as to further
ensure maximal
penetration and effectiveness of vibration therapy for acute vascular
disturbances. In this
alternative embodiment the vibration devices should optimally be operated in
phase to one
another (i..e. to avoid potential destructive interference of the therapeutic
signal). This
technique may be of particular relevance wherein an imaging technique to
direct vibration
therapy is not employed.
The disclosed "dual function" ultrasonic imaging system to direct (or target)
vibration therapy tnay also be embodied in a variety of ways.
For example, while the embodiment shown (apparatus) describes a direct, end to
end,
contact between a low frequency vibration source and an ultrasonic imaging
transducer (i. e.
such that the ultrasonic imaging transducer is acoustically linked to the
vibration source and
thereby transmits the generated low frequency vibration to the patient 20 via
a common
application surface), the vibration source and ultrasonic imaging probe may
alternatively be
mounted "side by side" by either a pivot assembly or an adjustable bracket (as
per technology
disclosed to US patent 5,919, 139), or by hand, which in either case would
reduce wear and
tear on the
CA 02540439 2006-01-27
WO 2005/023121 PCT/CA2004/001621
relatively expensive ultrasonic imaging probe as the ultrasonic imaging probe
itself
would not vibrate. The'variant "by hand" technique advantageously enables
additional
manual control (or maneuverability of the ultrasonic imaging transducer) which
is
generally required in ultrasonic imaging. In this altemative "side by side
vibration /
iniaging" embodiment, the degree of therapeutic vibration reaching the
targeted region
(and thereby the optimized placement of the vibration source or vibrator), may
be
gauged (or confiumed) by doppler or 2D / m mode interrogation of the invasive
structure
targeted.
Furthermore, it should be understood that while an ultrasonic imaging
transducer is preferably coupled to the active components of the preferred
vibrator 10
(or altematively the variant research vibrator for higher frequency
applications), these
arrangements are not critical and the ultrasonic imaging transducer may be
coupled to
any low frequency vibration source operable within the 1- 1000 Hz range
according to
the invention (regardless of the level of provided vibratory emission
control), as long as
the low frequency vibration wave form emitted does not significantly alter or
interfere
with the functioning of the imaging HFUS (mega hertz) wave form. The vibration
source in these cases (as the vibration eniitted will be advantageously
directed through a
sonic penetration window) needn't necessarily be operational at high force or
displacement amplitudes (i.e. to ensure therapeutic penetration), however high
displacement amplitude and force enablement is nonetheless preferred in
emergency
situations. Such vibration sources (as stated previously) may comprise but
should not be
limited to: linear stepper motors, linear stepper motors with displacement
amplification,
linear (non stepper) motors, ceramic servo motors coupled to either a rotary
(with cam)
or linear stage, rotary motors with rotary to linear conversion elements,
eccentrically
spinning weights, magnetostrictive actuators, voice coils, and shakers (e.g.
with or
without neodymium magnet transducers).
As will be apparent to those skilled in the art in light of the foregoing
disclosure,
many alterations and modifications are possible in the practice of this
invention without
departing from the spirit or scope thereof. Accordingly, the scope of the
invention is to
be construed in accordance with the substance defined by the following claims.
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